{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:29:48Z","timestamp":1788902988377,"version":"build-2803163510"},"reference-count":178,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009511","name":"Handong Global University Research Grant","doi-asserted-by":"publisher","award":["202400460001"],"award-info":[{"award-number":["202400460001"]}],"id":[{"id":"10.13039\/501100009511","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer is a heterogeneous disease at the cellular level and analyzing the genetic and molecular profile is essential for targeted therapy. Cancer cells continue to mutate, often resulting in drug resistance. In addition, cancers such as triple-negative breast cancer (TNBC) lack the target proteins used in some of the most effective therapies. This necessitates the identification of novel target proteins and biomarkers for effective treatment strategies. Ubiquitin E3 ligases are often differentially expressed in cancer cells, and numerous anticancer agents have been developed to inhibit them. SMURF2 is an E3 ligase that is differentially expressed in multiple cancer types. Although inhibiting upregulated SMURF2 may be strategically straightforward, enhancing the downregulated gene is often difficult. In addition, because E3 ligases ubiquitinate a variety of substrate proteins, targeting SMURF2 requires detailed analysis to achieve anticancer effect. This review discusses the dual role of SMURF2 in carcinogenesis and addresses the complex context-dependent function of SMURF2 in the various cellular pathways. In addition, resistance to existing cancer therapy related to SMURF2 and sensitivity mechanisms is discussed. Lastly, theranostic strategies for anticancer agents and biomarker development are suggested.<\/jats:p>","DOI":"10.3390\/ijms27031538","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T13:56:23Z","timestamp":1770213383000},"page":"1538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics"],"prefix":"10.3390","volume":"27","author":[{"given":"Joy","family":"Eom","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Life Science, Handong Global University, Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-3248","authenticated-orcid":false,"given":"Hae Ryung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Life Science, Handong Global University, Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e350","DOI":"10.1038\/bcj.2015.80","article-title":"A Phase 1 study of the novel gamma-secretase inhibitor PF-03084014 in patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma","volume":"5","author":"Papayannidis","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.2147\/OTT.S92945","article-title":"Prognostic value of Notch-1 expression in hepatocellular carcinoma: A meta-analysis","volume":"8","author":"Wu","year":"2015","journal-title":"Onco Targets Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E6457","DOI":"10.1073\/pnas.1614529113","article-title":"Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer","volume":"113","author":"Stoyanova","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1158\/1078-0432.CCR-21-3874","article-title":"A Phase Ib\/II Randomized Study of RO4929097, a Gamma-Secretase or Notch Inhibitor with or without Vismodegib, a Hedgehog Inhibitor, in Advanced Sarcoma","volume":"28","author":"Gounder","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1056\/NEJMoa2210140","article-title":"Nirogacestat, a gamma-Secretase Inhibitor for Desmoid Tumors","volume":"388","author":"Gounder","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41419-022-05133-9","article-title":"AL101, a gamma-secretase inhibitor, has potent antitumor activity against adenoid cystic carcinoma with activated NOTCH signaling","volume":"13","author":"Ferrarotto","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10637-020-01001-5","article-title":"A phase 1 study of crenigacestat (LY3039478), the Notch inhibitor, in Japanese patients with advanced solid tumors","volume":"39","author":"Doi","year":"2021","journal-title":"Invest. New Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1158\/2767-9764.CRC-23-0333","article-title":"A Phase I Study of the Pan-Notch Inhibitor CB-103 for Patients with Advanced Adenoid Cystic Carcinoma and Other Tumors","volume":"3","author":"Hanna","year":"2023","journal-title":"Cancer Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41392-024-01828-x","article-title":"Notch signaling pathway in cancer: From mechanistic insights to targeted therapies","volume":"9","author":"Shi","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nm.1900","article-title":"Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia","volume":"15","author":"Real","year":"2009","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17761","DOI":"10.1073\/pnas.1114669108","article-title":"Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1182\/blood-2013-08-355818","article-title":"Notch signaling: Switching an oncogene to a tumor suppressor","volume":"123","author":"Lobry","year":"2014","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155763","DOI":"10.1016\/j.prp.2024.155763","article-title":"Molecular and pathological landscape of the AT-rich interaction domain 1A (ARID1A) mutation in hepatocellular carcinoma","volume":"266","author":"Li","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.ccell.2017.10.007","article-title":"Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer","volume":"32","author":"Sun","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.21037\/tcr-23-645","article-title":"The stage-dependent prognostic role of ARID1A in hepatocellular carcinoma","volume":"12","author":"Zhou","year":"2023","journal-title":"Transl. Cancer Res."},{"key":"ref_19","first-page":"50","article-title":"Targeting the ubiquitin pathway for cancer treatment","volume":"1855","author":"Liu","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-020-0107-0","article-title":"The role of ubiquitination in tumorigenesis and targeted drug discovery","volume":"5","author":"Deng","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5979","DOI":"10.1021\/jm400487c","article-title":"Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development","volume":"56","author":"Ding","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1111\/cas.14875","article-title":"Safety and pharmacokinetics of milademetan, a MDM2 inhibitor, in Japanese patients with solid tumors: A phase I study","volume":"112","author":"Takahashi","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_23","first-page":"2895","article-title":"Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions","volume":"21","author":"Cheng","year":"2001","journal-title":"Anticancer. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4491","DOI":"10.1158\/1078-0432.CCR-08-0024","article-title":"Phase II trial of curcumin in patients with advanced pancreatic cancer","volume":"14","author":"Dhillon","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000441148","article-title":"The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study","volume":"90","author":"Mahammedi","year":"2016","journal-title":"Oncology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s43556-021-00043-2","article-title":"E3 ubiquitin ligases: Styles, structures and functions","volume":"2","author":"Yang","year":"2021","journal-title":"Mol. Biomed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s42003-022-03060-1","article-title":"Non-proteolytic ubiquitylation in cellular signaling and human disease","volume":"5","author":"Liao","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.18632\/oncotarget.2431","article-title":"Screening for E3-ubiquitin ligase inhibitors: Challenges and opportunities","volume":"5","author":"Landre","year":"2014","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16019","DOI":"10.1038\/celldisc.2016.19","article-title":"The ERK signaling target RNF126 regulates anoikis resistance in cancer cells by changing the mitochondrial metabolic flux","volume":"2","author":"Yoshino","year":"2016","journal-title":"Cell Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13058-022-01586-0","article-title":"Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors","volume":"24","author":"Pan","year":"2022","journal-title":"Breast Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.molcel.2014.05.025","article-title":"Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6","volume":"55","author":"Gutierrez","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1016\/j.cell.2023.05.035","article-title":"Mechanisms of readthrough mitigation reveal principles of GCN1-mediated translational quality control","volume":"186","author":"Muller","year":"2023","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.molcel.2020.06.023","article-title":"RNF126-Mediated Reubiquitination Is Required for Proteasomal Degradation of p97-Extracted Membrane Proteins","volume":"79","author":"Hu","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10917","DOI":"10.2147\/OTT.S271855","article-title":"Overexpression of RNF126 Promotes the Development of Colorectal Cancer via Enhancing p53 Ubiquitination and Degradation","volume":"13","author":"Wang","year":"2020","journal-title":"Onco Targets Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.2217\/bmm-2020-0798","article-title":"Overexpression of RNF126 is associated with poor prognosis and contributes to the progression of lung adenocarcinoma","volume":"15","author":"Sun","year":"2021","journal-title":"Biomark. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1007\/s13577-022-00782-6","article-title":"RNF126 contributes to stem cell-like properties and metastasis in hepatocellular carcinoma through ubiquitination and degradation of LKB1","volume":"35","author":"Huang","year":"2022","journal-title":"Hum. Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.21873\/anticanres.14078","article-title":"RNF126 as a Marker of Prognosis and Proliferation of Gastric Cancer","volume":"40","author":"Migita","year":"2020","journal-title":"Anticancer. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vu, A.D., Mori, S., Akamatsu, K., Nakayama, J., and Sakamoto, T. (2025). Ring-Finger Protein 126 (RNF126) Promotes Anoikis Resistance and Peritoneal Colonization in Ovarian Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262412183"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23847","DOI":"10.1038\/s41598-025-04629-6","article-title":"Ring-finger protein RNF126 promotes prostate cancer progression via regulation of MBNL1","volume":"15","author":"Jiang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e31259","DOI":"10.1002\/jcp.31259","article-title":"ZNF263 cooperates with ZNF31 to promote the drug resistance and EMT of pancreatic cancer through transactivating RNF126","volume":"239","author":"Zhang","year":"2024","journal-title":"J. Cell Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1158\/0008-5472.CAN-12-0562","article-title":"E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation","volume":"73","author":"Zhi","year":"2013","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41419-021-03521-1","article-title":"E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability","volume":"12","author":"Xu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/onc.2015.198","article-title":"RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expression","volume":"35","author":"Wang","year":"2016","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bbrc.2021.08.011","article-title":"CHFR-mediated degradation of RNF126 confers sensitivity to PARP inhibitors in triple-negative breast cancer cells","volume":"573","author":"Wu","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shah, P.A., Boutros-Suleiman, S., Emanuelli, A., Paolini, B., Levy-Cohen, G., and Blank, M. (2022). The Emerging Role of E3 Ubiquitin Ligase SMURF2 in the Regulation of Transcriptional Co-Repressor KAP1 in Untransformed and Cancer Cells and Tissues. Cancers, 14.","DOI":"10.3390\/cancers14071607"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/S1097-2765(00)00134-9","article-title":"Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation","volume":"6","author":"Kavsak","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tzavlaki, K., and Moustakas, A. (2020). TGF-beta Signaling. Biomolecules, 10.","DOI":"10.3390\/biom10030487"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1172\/JCI0215234","article-title":"Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases","volume":"109","author":"Muraoka","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"16709","DOI":"10.1074\/jbc.275.22.16709","article-title":"Induction of platelet-derived growth factor B-chain expression by transforming growth factor-beta involves transactivation by Smads","volume":"275","author":"Taylor","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, A., Hou, C., Chen, H., Zong, X., and Zong, P. (2016). Genetics and Epigenetics of Glioblastoma: Applications and Overall Incidence of IDH1 Mutation. Front. Oncol., 6.","DOI":"10.3389\/fonc.2016.00016"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1186\/s13046-019-1343-4","article-title":"TFEB-driven autophagy potentiates TGF-beta induced migration in pancreatic cancer cells","volume":"38","author":"He","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1091\/mbc.e04-08-0658","article-title":"TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition","volume":"16","author":"Valcourt","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R187","DOI":"10.1186\/bcr640","article-title":"Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line","volume":"5","author":"Xie","year":"2003","journal-title":"Breast Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"26750","DOI":"10.1074\/jbc.270.45.26750","article-title":"Transforming growth factor beta activates the promoter of cyclin-dependent kinase inhibitor p15INK4B through an Sp1 consensus site","volume":"270","author":"Li","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1073\/pnas.92.12.5545","article-title":"Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism","volume":"92","author":"Datto","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S1097-2765(03)00109-6","article-title":"A self-enabling TGFbeta response coupled to stress signaling: Smad engages stress response factor ATF3 for Id1 repression in epithelial cells","volume":"11","author":"Kang","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_57","first-page":"3088","article-title":"Selective inhibition of growth-related gene expression in murine keratinocytes by transforming growth factor beta","volume":"8","author":"Coffey","year":"1988","journal-title":"Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrc3638","article-title":"The ID proteins: Master regulators of cancer stem cells and tumour aggressiveness","volume":"14","author":"Lasorella","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10017","DOI":"10.1128\/MCB.25.22.10017-10028.2005","article-title":"Transforming growth factor beta-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells","volume":"25","author":"Ohgushi","year":"2005","journal-title":"Mol. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11","DOI":"10.4161\/cc.8.1.7291","article-title":"Transforming growth factor beta (TGFbeta)-induced apoptosis: The rise & fall of Bim","volume":"8","author":"Ramesh","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/cdd.2008.183","article-title":"TGF-beta induces apoptosis in human B cells by transcriptional regulation of BIK and BCL-XL","volume":"16","author":"Spender","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.canlet.2021.08.002","article-title":"The transformation of cancer-associated fibroblasts: Current perspectives on the role of TGF-beta in CAF mediated tumor progression and therapeutic resistance","volume":"520","author":"Sarkar","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Baba, A.B., Rah, B., Bhat, G.R., Mushtaq, I., Parveen, S., Hassan, R., Hameed Zargar, M., and Afroze, D. (2022). Transforming Growth Factor-Beta (TGF-beta) Signaling in Cancer-A Betrayal Within. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.791272"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cell.2008.01.046","article-title":"TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4","volume":"133","author":"Padua","year":"2008","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/cr.2009.5","article-title":"TGF-beta-induced epithelial to mesenchymal transition","volume":"19","author":"Xu","year":"2009","journal-title":"Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.3892\/ijo.2014.2310","article-title":"JAK\/STAT3 signaling is required for TGF-beta-induced epithelial-mesenchymal transition in lung cancer cells","volume":"44","author":"Liu","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hao, Y., Baker, D., and Ten Dijke, P. (2019). TGF-beta-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112767"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1016\/j.cell.2023.07.036","article-title":"TGF-beta signaling in health and disease","volume":"186","author":"Massague","year":"2023","journal-title":"Cell"},{"key":"ref_69","first-page":"1413","article-title":"Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta\/Smad signaling","volume":"63","author":"Baldwin","year":"2003","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1038\/onc.2013.102","article-title":"Inactivation of TGF-beta signaling and loss of PTEN cooperate to induce colon cancer in vivo","volume":"33","author":"Yu","year":"2014","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Bailey, K.L., Agarwal, E., Chowdhury, S., Luo, J., Brattain, M.G., Black, J.D., and Wang, J. (2017). TGFbeta\/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in colon cancer cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176096"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"David, D., Surendran, A., Thulaseedharan, J.V., and Nair, A.S. (2018). Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4188-x"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5495","DOI":"10.1038\/s41598-022-09390-8","article-title":"Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer","volume":"12","author":"Sato","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.7554\/eLife.02555","article-title":"Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception","volume":"3","author":"Yue","year":"2014","journal-title":"eLife"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41420-024-02260-4","article-title":"SMURF1 and SMURF2 directly target GLI1 for ubiquitination and proteasome-dependent degradation","volume":"10","author":"Bordin","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"18485","DOI":"10.1074\/jbc.RA120.014179","article-title":"Phosphorylation of SMURF2 by ATM exerts a negative feedback control of DNA damage response","volume":"295","author":"Tang","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1016\/j.celrep.2019.08.031","article-title":"A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis","volume":"28","author":"Du","year":"2019","journal-title":"Cell Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/j.1474-9726.2011.00746.x","article-title":"Smurf2-mediated ubiquitination and degradation of Id1 regulates p16 expression during senescence","volume":"10","author":"Kong","year":"2011","journal-title":"Aging Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1101\/gad.1253004","article-title":"Smurf2 up-regulation activates telomere-dependent senescence","volume":"18","author":"Zhang","year":"2004","journal-title":"Genes. Dev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s42003-021-02950-0","article-title":"SMURF2 phosphorylation at Thr249 modifies glioma stemness and tumorigenicity by regulating TGF-beta receptor stability","volume":"5","author":"Hiraiwa","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Golan-Cancela, I., and Caja, L. (2024). The TGF-beta Family in Glioblastoma. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021067"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.1038\/emboj.2011.393","article-title":"Ablation of Smurf2 reveals an inhibition in TGF-beta signalling through multiple mono-ubiquitination of Smad3","volume":"30","author":"Tang","year":"2011","journal-title":"EMBO J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Emanuelli, A., Manikoth Ayyathan, D., Koganti, P., Shah, P.A., Apel-Sarid, L., Paolini, B., Detroja, R., Frenkel-Morgenstern, M., and Blank, M. (2019). Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer. Cancers, 11.","DOI":"10.3390\/cancers11040556"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.1126\/scisignal.aav5183","article-title":"Specificity, versatility, and control of TGF-beta family signaling","volume":"12","author":"Derynck","year":"2019","journal-title":"Sci. Signal"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"22053","DOI":"10.1101\/cshperspect.a022053","article-title":"Signaling Receptors for TGF-beta Family Members","volume":"8","author":"Heldin","year":"2016","journal-title":"Cold Spring Harb. Perspect Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1073\/pnas.98.3.974","article-title":"Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase","volume":"98","author":"Zhang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","first-page":"7162","article-title":"High-level expression of the Smad ubiquitin ligase Smurf2 correlates with poor prognosis in patients with esophageal squamous cell carcinoma","volume":"62","author":"Fukuchi","year":"2002","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/S0002-9440(10)63521-3","article-title":"Ubiquitin-dependent degradation of Smad2 is increased in the glomeruli of rats with anti-thymocyte serum nephritis","volume":"163","author":"Togawa","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"10140","DOI":"10.1038\/s41598-022-14448-8","article-title":"Smurf2 inhibition enhances chemotherapy and radiation sensitivity in non-small-cell lung cancer","volume":"12","author":"Chaudhary","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"36818","DOI":"10.1074\/jbc.C000580200","article-title":"Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling","volume":"275","author":"Lin","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a022129","article-title":"Non-Smad Signaling Pathways of the TGF-beta Family","volume":"9","author":"Zhang","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"C311","DOI":"10.1152\/ajpcell.2001.281.1.C311","article-title":"Smad4 mediates activation of mitogen-activated protein kinases by TGF-beta in pancreatic acinar cells","volume":"281","author":"Simeone","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1242\/jcs.076505","article-title":"TbetaRI\/Alk5-independent TbetaRII signaling to ERK1\/2 in human skin cells according to distinct levels of TbetaRII expression","volume":"124","author":"Bandyopadhyay","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1073\/pnas.89.4.1512","article-title":"A human Id-like helix-loop-helix protein expressed during early development","volume":"89","author":"Biggs","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","first-page":"5603","article-title":"Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins","volume":"11","author":"Sun","year":"1991","journal-title":"Mol. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12964-016-0161-y","article-title":"The Id-protein family in developmental and cancer-associated pathways","volume":"15","author":"Roschger","year":"2017","journal-title":"Cell Commun. Signal"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.7150\/ijbs.80979","article-title":"SMURF2 facilitates ubiquitin-mediated degradation of ID2 to attenuate lung cancer cell proliferation","volume":"19","author":"Han","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1083\/jcb.201109045","article-title":"JunB contributes to Id2 repression and the epithelial-mesenchymal transition in response to transforming growth factor-beta","volume":"196","author":"Gervasi","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrc2608","article-title":"DNA topoisomerase II and its growing repertoire of biological functions","volume":"9","author":"Nitiss","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1158\/0008-5472.CAN-16-2828","article-title":"Smurf2-Mediated Stabilization of DNA Topoisomerase IIalpha Controls Genomic Integrity","volume":"77","author":"Emanuelli","year":"2017","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Pampalona, J., Roscioli, E., Silkworth, W.T., Bowden, B., Genesca, A., Tusell, L., and Cimini, D. (2016). Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147420"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Koganti, P., Levy-Cohen, G., and Blank, M. (2018). Smurfs in Protein Homeostasis, Signaling, and Cancer. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00295"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nm.2596","article-title":"A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20","volume":"18","author":"Blank","year":"2012","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s41419-023-06025-2","article-title":"Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma","volume":"14","author":"Li","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sigafoos, A.N., Paradise, B.D., and Fernandez-Zapico, M.E. (2021). Hedgehog\/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease. Cancers, 13.","DOI":"10.3390\/cancers13143410"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/dgd.12756","article-title":"The many faces of the E3 ubiquitin ligase, RNF220, in neural development and beyond","volume":"64","author":"Ma","year":"2022","journal-title":"Dev. Growth Differ."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"21185","DOI":"10.1073\/pnas.0909471106","article-title":"Shh signaling regulates adrenocortical development and identifies progenitors of steroidogenic lineages","volume":"106","author":"King","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Bai, Y., and Ying, Y. (2020). The Post-translational Modifications of Smurf2 in TGF-beta Signaling. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00128"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18404","DOI":"10.1073\/pnas.1003023107","article-title":"Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity","volume":"107","author":"Chong","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"41364","DOI":"10.1038\/srep41364","article-title":"The Nedd8 Non-Covalent Binding Region in the Smurf HECT Domain is Critical to its Ubiquitn Ligase Function","volume":"7","author":"He","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.molcel.2013.07.014","article-title":"TRAF4 promotes TGF-beta receptor signaling and drives breast cancer metastasis","volume":"51","author":"Zhang","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"164004","DOI":"10.1242\/dev.164004","article-title":"The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis","volume":"145","author":"Iezaki","year":"2018","journal-title":"Development"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"21660","DOI":"10.1073\/pnas.0911316106","article-title":"The glucose-responsive transcription factor ChREBP contributes to glucose-dependent anabolic synthesis and cell proliferation","volume":"106","author":"Tong","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"14745","DOI":"10.1074\/jbc.RA119.007508","article-title":"The ubiquitination ligase SMURF2 reduces aerobic glycolysis and colorectal cancer cell proliferation by promoting ChREBP ubiquitination and degradation","volume":"294","author":"Li","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Martins, S.F., Amorim, R., Viana-Pereira, M., Pinheiro, C., Costa, R.F., Silva, P., Couto, C., Alves, S., Fernandes, S., and Vilaca, S. (2016). Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2566-9"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"714","DOI":"10.3892\/ijo.2015.3281","article-title":"RhoA is associated with invasion and poor prognosis in colorectal cancer","volume":"48","author":"Jeong","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.omto.2021.11.007","article-title":"AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA","volume":"23","author":"Wu","year":"2021","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.canlet.2019.01.039","article-title":"Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression","volume":"448","author":"Yu","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature06781","article-title":"SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis","volume":"452","author":"Han","year":"2008","journal-title":"Nature"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.7150\/ijbs.68995","article-title":"CBX3 Regulated by YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression","volume":"18","author":"Zhang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Dinh, N.T.M., Nguyen, T.M., Park, M.K., and Lee, C.H. (2024). Y-Box Binding Protein 1: Unraveling the Multifaceted Role in Cancer Development and Therapeutic Potential. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020717"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"110864","DOI":"10.1016\/j.isci.2024.110864","article-title":"RRM2 promotes liver metastasis of pancreatic cancer by stabilizing YBX1 and activating the TGF-beta pathway","volume":"27","author":"Du","year":"2024","journal-title":"iScience"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/pcmr.12370","article-title":"Microphthalmia-associated transcription factor in melanoma development and MAP-kinase pathway targeted therapy","volume":"28","author":"Wellbrock","year":"2015","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/onc.2012.25","article-title":"Combination of MEK and SRC inhibition suppresses melanoma cell growth and invasion","volume":"32","author":"Ferguson","year":"2013","journal-title":"Oncogene"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/jnci\/djs471","article-title":"Effect of SMURF2 targeting on susceptibility to MEK inhibitors in melanoma","volume":"105","author":"Smith","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Kordass, T., Weber, C.E., Oswald, M., Ast, V., Bernhardt, M., Novak, D., Utikal, J., Eichmuller, S.B., and Konig, R. (2016). SOX5 is involved in balanced MITF regulation in human melanoma cells. BMC Med. Genom., 9.","DOI":"10.1186\/s12920-016-0170-0"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1101\/gad.406406","article-title":"Mitf regulation of Dia1 controls melanoma proliferation and invasiveness","volume":"20","author":"Carreira","year":"2006","journal-title":"Genes. Dev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"17996","DOI":"10.1074\/jbc.M112.358341","article-title":"Expression of microphthalmia-associated transcription factor (MITF), which is critical for melanoma progression, is inhibited by both transcription factor GLI2 and transforming growth factor-beta","volume":"287","author":"Pierrat","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"6254","DOI":"10.1073\/pnas.1606027113","article-title":"BPTF transduces MITF-driven prosurvival signals in melanoma cells","volume":"113","author":"Dar","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.molcel.2008.11.002","article-title":"Inhibition of PAX3 by TGF-beta modulates melanocyte viability","volume":"32","author":"Yang","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"188078","DOI":"10.1242\/dev.188078","article-title":"RNF220 is required for cerebellum development and regulates medulloblastoma progression through epigenetic modulation of Shh signaling","volume":"147","author":"Ma","year":"2020","journal-title":"Development"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1242\/jcs.040493","article-title":"H-Ras is degraded by Wnt\/beta-catenin signaling via beta-TrCP-mediated polyubiquitylation","volume":"122","author":"Kim","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"ra30","DOI":"10.1126\/scisignal.2002242","article-title":"Ras stabilization through aberrant activation of Wnt\/beta-catenin signaling promotes intestinal tumorigenesis","volume":"5","author":"Jeong","year":"2012","journal-title":"Sci. Signal"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tig.2012.06.001","article-title":"Nuclear lamin functions and disease","volume":"28","author":"Adam","year":"2012","journal-title":"Trends Genet."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1593\/neo.14184","article-title":"KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated beta-TrCP1 degradation","volume":"16","author":"Shukla","year":"2014","journal-title":"Neoplasia"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.semcancer.2019.12.023","article-title":"The functions and regulation of Smurfs in cancers","volume":"67","author":"Fu","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1593\/neo.11632","article-title":"Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2","volume":"13","author":"Ray","year":"2011","journal-title":"Neoplasia"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"12661","DOI":"10.1074\/jbc.RA120.013519","article-title":"Ubiquitin ligase SMURF2 enhances epidermal growth factor receptor stability and tyrosine-kinase inhibitor resistance","volume":"295","author":"Ray","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1016\/j.cllc.2019.12.003","article-title":"Tyrosine Kinase Inhibitors for the Treatment of EGFR Mutation-Positive Non-Small-Cell Lung Cancer: A Clash of the Generations","volume":"21","author":"Shah","year":"2020","journal-title":"Clin. Lung Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.tcb.2013.11.002","article-title":"EGF receptor trafficking: Consequences for signaling and cancer","volume":"24","author":"Tomas","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Sung, W.J., Kim, D., Zhu, A., Cho, N., Yoo, H.M., Noh, J.H., Kim, K.M., Lee, H.S., and Hong, J. (2022). The lysosome as a novel therapeutic target of EGFR-mediated tumor inflammation. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1050758"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Betriu, N., Andreeva, A., and Semino, C.E. (2021). Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells. Cancers, 13.","DOI":"10.3390\/cancers13184504"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nm.2619","article-title":"USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the activation of TGF-beta signaling in glioblastoma","volume":"18","author":"Eichhorn","year":"2012","journal-title":"Nat. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1002\/1878-0261.12581","article-title":"MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-beta receptor I ubiquitination","volume":"13","author":"Chae","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1158\/0008-5472.CAN-08-1463","article-title":"Smad ubiquitination regulatory factor 2 promotes metastasis of breast cancer cells by enhancing migration and invasiveness","volume":"69","author":"Jin","year":"2009","journal-title":"Cancer Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1747-1028-9-2","article-title":"Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner","volume":"9","author":"David","year":"2014","journal-title":"Cell Div."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"447","DOI":"10.2165\/00003495-199754030-00009","article-title":"Gemcitabine. A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer","volume":"54","author":"Noble","year":"1997","journal-title":"Drugs"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.3892\/ijo.2015.3076","article-title":"miR-15b promotes epithelial-mesenchymal transition by inhibiting SMURF2 in pancreatic cancer","volume":"47","author":"Zhang","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1158\/0008-5472.CAN-08-4312","article-title":"Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway","volume":"69","author":"Wang","year":"2009","journal-title":"Cancer Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.pharmthera.2016.02.008","article-title":"Cancer stem cells and chemoresistance: The smartest survives the raid","volume":"160","author":"Zhao","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Funamizu, N., Honjo, M., Tamura, K., Sakamoto, K., Ogawa, K., and Takada, Y. (2023). microRNAs Associated with Gemcitabine Resistance via EMT, TME, and Drug Metabolism in Pancreatic Cancer. Cancers, 15.","DOI":"10.3390\/cancers15041230"},{"key":"ref_152","unstructured":"Gold, J.M., and Raja, A. (2025). Cisplatin. StatPearls, StatPearls."},{"key":"ref_153","first-page":"654","article-title":"Cisplatin-Based Chemotherapy of Human Cancers","volume":"11","author":"Brown","year":"2019","journal-title":"J. Cancer Sci. Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ctrv.2016.01.003","article-title":"Cisplatin in the modern era: The backbone of first-line chemotherapy for non-small cell lung cancer","volume":"44","author":"Fennell","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s10637-013-0004-2","article-title":"Phase 1 study of sorafenib in combination with bortezomib in patients with advanced malignancies","volume":"31","author":"Kumar","year":"2013","journal-title":"Invest. New Drugs"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.3892\/ijo.2014.2545","article-title":"Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2","volume":"45","author":"Wang","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_157","first-page":"4618","article-title":"Adenovirus-mediated human topoisomerase IIalpha gene transfer increases the sensitivity of etoposide-resistant human breast cancer cells","volume":"59","author":"Zhou","year":"1999","journal-title":"Cancer Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1200\/JCO.1986.4.6.982","article-title":"Etoposide (VP-16) and cisplatin in previously treated small-cell lung cancer: Clinical trial and in vitro correlates","volume":"4","author":"Batist","year":"1986","journal-title":"J. Clin. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1016\/j.ejca.2014.10.006","article-title":"Outcome of 3-day bleomycin, etoposide and cisplatin chemotherapeutic regimen for patients with malignant ovarian germ cell tumours: A Taiwanese Gynecologic Oncology Group study","volume":"50","author":"Chen","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.18632\/oncotarget.3077","article-title":"Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer","volume":"6","author":"Kirk","year":"2015","journal-title":"Oncotarget"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1042\/bj3190307","article-title":"Transfection of human topoisomerase II alpha into etoposide-resistant cells: Transient increase in sensitivity followed by down-regulation of the endogenous gene","volume":"319","author":"Asano","year":"1996","journal-title":"Biochem. J."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1054\/bjoc.2001.1966","article-title":"Enhanced etoposide sensitivity following adenovirus-mediated human topoisomerase IIalpha gene transfer is independent of topoisomerase IIbeta","volume":"85","author":"Zhou","year":"2001","journal-title":"Br. J. Cancer"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"9053","DOI":"10.1073\/pnas.0803513105","article-title":"Topoisomerase levels determine chemotherapy response in vitro and in vivo","volume":"105","author":"Burgess","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6589","DOI":"10.1007\/s11033-021-06665-7","article-title":"Regulation of topoisomerase II stability and activity by ubiquitination and SUMOylation: Clinical implications for cancer chemotherapy","volume":"48","author":"Ma","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.3174\/ajnr.A2619","article-title":"Trastuzumab (herceptin)","volume":"32","author":"Gemmete","year":"2011","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.cell.2019.08.027","article-title":"Herceptin: A First Assault on Oncogenes that Launched a Revolution","volume":"179","author":"Sawyers","year":"2019","journal-title":"Cell"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41571-019-0268-3","article-title":"HER2-targeted therapies\u2014A role beyond breast cancer","volume":"17","author":"Oh","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1038\/s41418-019-0328-3","article-title":"TRAF4 positively regulates the osteogenic differentiation of mesenchymal stem cells by acting as an E3 ubiquitin ligase to degrade Smurf2","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1038\/s41388-022-02415-6","article-title":"TRAF4 hyperactivates HER2 signaling and contributes to Trastuzumab resistance in HER2-positive breast cancer","volume":"41","author":"Gu","year":"2022","journal-title":"Oncogene"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13046-025-03391-x","article-title":"MicroRNA in cancer therapy: Breakthroughs and challenges in early clinical applications","volume":"44","author":"Martino","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Furuta, M., Kozaki, K., Tanimoto, K., Tanaka, S., Arii, S., Shimamura, T., Niida, A., Miyano, S., and Inazawa, J. (2013). The tumor-suppressive miR-497-195 cluster targets multiple cell-cycle regulators in hepatocellular carcinoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060155"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1182\/blood.2020007591","article-title":"MicroRNA-497\/195 is tumor suppressive and cooperates with CDKN2A\/B in pediatric acute lymphoblastic leukemia","volume":"138","author":"Boldrin","year":"2021","journal-title":"Blood"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1158\/1541-7786.MCR-23-1075","article-title":"miR-497 Target Gene Regulatory Network in Angiosarcoma","volume":"22","author":"Benton","year":"2024","journal-title":"Mol. Cancer Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.3892\/ijo.2025.5727","article-title":"Curcumin inhibits the activity of ubiquitin ligase Smurf2 to promote NLRP3-dependent pyroptosis in non-small cell lung cancer cells","volume":"66","author":"Xi","year":"2025","journal-title":"Int. J. Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"e4885","DOI":"10.1002\/pro.4885","article-title":"Structural and functional validation of a highly specific Smurf2 inhibitor","volume":"33","author":"Tessier","year":"2024","journal-title":"Protein Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"16736","DOI":"10.1073\/pnas.1412152111","article-title":"Peptide and small molecule inhibitors of HECT-type ubiquitin ligases","volume":"111","author":"Mund","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1002\/cbic.201800321","article-title":"Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities","volume":"19","author":"Chen","year":"2018","journal-title":"Chembiochem"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"8","DOI":"10.17305\/bjbms.2018.2756","article-title":"The role of the Hedgehog signaling pathway in cancer: A comprehensive review","volume":"18","author":"Skoda","year":"2018","journal-title":"Bosn. J. Basic Med. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1538\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T10:45:54Z","timestamp":1770633954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":178,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031538"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031538","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]}}}