{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:58:48Z","timestamp":1790963928491,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-\u03b2 signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-\u03b2 signals through SMAD proteins, which are intracellular molecules that transmit TGF-\u03b2 signals from the cell membrane to the nucleus. Alterations in the TGF-\u03b2 pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-\u03b2 signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-\u03b2 influences metastasis development. TGF-\u03b2 promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-\u03b2 affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-\u03b2 in mCRC patients, aiming to identify new therapeutic options.<\/jats:p>","DOI":"10.3390\/ijms25137400","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["TGF-\u03b2 Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0782-8778","authenticated-orcid":false,"given":"Morena","family":"Fasano","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Pirozzi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Carmen","family":"Miceli","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Cocule","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2408-6091","authenticated-orcid":false,"given":"Michele","family":"Caraglia","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"},{"name":"Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, Contrada Camporeale, 83031 Ariano Irpino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6989-010X","authenticated-orcid":false,"given":"Mariarosaria","family":"Boccellino","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Vitale","sequence":"additional","affiliation":[{"name":"Oncology Operative Unit, Hospital of Frattamaggiore, ASLNA2NORD, Frattamaggiore, 80027 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Falco","sequence":"additional","affiliation":[{"name":"Oncology Operative Unit, Hospital of Frattamaggiore, ASLNA2NORD, Frattamaggiore, 80027 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Farese","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Zotta","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Ciardiello","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-8060","authenticated-orcid":false,"given":"Raffaele","family":"Addeo","sequence":"additional","affiliation":[{"name":"Oncology Operative Unit, Hospital of Frattamaggiore, ASLNA2NORD, Frattamaggiore, 80027 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00441-017-2633-9","article-title":"Role of TGF-\u03b2 in metastatic colon cancer: It is finally time for targeted therapy","volume":"370","author":"Villalba","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/gutjnl-2015-310912","article-title":"Global patterns and trends in colorectal cancer incidence and mortality","volume":"66","author":"Arnold","year":"2017","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.annonc.2020.06.022","article-title":"Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Tabernero","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/ags3.12071","article-title":"Recent advances in treatment for colorectal liver metastasis","volume":"2","author":"Oki","year":"2018","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/1878-0261.12018","article-title":"Determinants of metastatic competency in colorectal cancer","volume":"11","author":"Tauriello","year":"2017","journal-title":"Mol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Itatani, Y., Kawada, K., and Sakai, Y. (2019). Transforming Growth Factor-\u03b2 Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235822"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.dld.2022.01.131","article-title":"Possible role of nuclear factor erythroid 2-related factor 2 in the progression of human colon precancerous lesions","volume":"54","author":"Polimeno","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","article-title":"Mechanisms of TGF-\u03b2 signaling from cell membrane to the nucleus","volume":"113","author":"Shi","year":"2003","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.7150\/ijbs.23230","article-title":"The role of TGF-\u03b2\/SMAD4 signaling in cancer","volume":"14","author":"Zhao","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, X., Wu, Y., and Tian, T. (2022). TGF-\u03b2 Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214436"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/jso.20517","article-title":"Expression of DPC4\/Smad4 gene in stone-containing intrahepatic bile duct","volume":"94","author":"Lee","year":"2006","journal-title":"J. Surg. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/MPA.0b013e31819d7415","article-title":"Identification and characterization of a novel anticancer agent with selectivity against deleted in pancreatic cancer locus 4 (DPC4)-deficient pancreatic and colon cancer cells","volume":"38","author":"Wang","year":"2009","journal-title":"Pancreas"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41568-021-00413-6","article-title":"Overcoming TGF\u03b2-mediated immune evasion in cancer","volume":"22","author":"Tauriello","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1126\/science.1071809","article-title":"Signal transduction by the TGF-\u03b2 superfamily","volume":"296","author":"Attisano","year":"2002","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrm3434","article-title":"TGF\u03b2 signalling in context","volume":"13","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Huang, Y.H., Lin, P.C., Su, W.C., Chan, R.H., Chen, P.C., Lin, B.W., Shen, M.R., Chen, S.H., and Yeh, Y.M. (2021). Association between Altered Oncogenic Signaling Pathways and Overall Survival of Patients with Metastatic Colorectal Cancer. Diagnostics, 11.","DOI":"10.3390\/diagnostics11122308"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ceb.2014.09.001","article-title":"Signaling pathway cooperation in TGF-\u03b2-induced epithelial-mesenchymal transition","volume":"3","author":"Derynck","year":"2014","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Heldin, C.H., and Moustakas, A. (2016). Signaling Receptors for TGF-\u03b2 Family Members. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a022053"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jamcollsurg.2021.05.027","article-title":"Genomic Sequencing and Insight into Clinical Heterogeneity and Prognostic Pathway Genes in Patients with Metastatic Colorectal Cancer","volume":"233","author":"Kawaguchi","year":"2021","journal-title":"J. Am. Coll. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.trecan.2016.11.008","article-title":"Targeting TGF-\u03b2 Signaling in Cancer","volume":"3","author":"Colak","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cancergencyto.2004.05.008","article-title":"Significance of mutations in TGFBR2 and BAX in neoplastic progression and patient outcome in sporadic colorectal tumors with high-frequency microsatellite instability","volume":"157","author":"Nejda","year":"2005","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive molecular characterization of human colon and rectal cancer","volume":"487","author":"Muzny","year":"2012","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Troncone, E., and Monteleone, G. (2019). Smad7 and Colorectal Carcinogenesis: A Double-Edged Sword. Cancers, 11.","DOI":"10.3390\/cancers11050612"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/bjc.2014.560","article-title":"The BMP pathway either enhances or inhibits the Wnt pathway depending on the SMAD4 and p53 status in CRC","volume":"112","author":"Voorneveld","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1158\/0008-5472.CAN-09-3269","article-title":"Smad4 inactivation promotes malignancy and drug resistance of colon cancer","volume":"71","author":"Papageorgis","year":"2011","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1053\/j.gastro.2016.10.015","article-title":"Transforming Growth Factor \u03b2 Superfamily Signaling in Development of Colorectal Cancer","volume":"152","author":"Jung","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S1359-6101(99)00026-X","article-title":"Role of Ras and Mapks in TGF\u03b2 signaling","volume":"11","author":"Mulder","year":"2000","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.1016\/S0021-9258(18)42722-6","article-title":"Activation of p21ras by Transforming Growth Factor \u03b2 in Epithelial Cells","volume":"267","author":"Mulder","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_29","unstructured":"Miyazono, K., and Derynck, R. (2007). TGF-\u03b2 signaling in epithelial-mesenchymal transition and invasion and metastasis. The TGF-\u0392 Family, Cold Spring Harbor Laboratory Press."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1002\/mco2.144","article-title":"Epithelial-mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities","volume":"3","author":"Huang","year":"2022","journal-title":"MedComm"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"716","DOI":"10.3390\/cancers30100716","article-title":"Cancer Stem Cells and Epithelial-to-Mesenchymal Transition (EMT)-Phenotypic Cells: Are They Cousins or Twins?","volume":"3","author":"Kong","year":"2011","journal-title":"Cancers"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6813","DOI":"10.1002\/jcb.26905","article-title":"The enigmatic role of matrix metalloproteinases in epithelial-to-mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects","volume":"120","author":"Ricci","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6195","DOI":"10.1038\/s41388-018-0378-x","article-title":"Epithelial-mesenchymal-transition-inducing transcription factors: New targets for tackling chemoresistance in cancer?","volume":"37","author":"Baker","year":"2018","journal-title":"Oncogene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1146\/annurev.cellbio.19.011102.111135","article-title":"Cadherins as modulators of cellular phenotype","volume":"19","author":"Wheelock","year":"2003","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_35","first-page":"1131","article-title":"Down-regulation of E-cadherin in mouse skin carcinoma cells enhances a migratory and invasive phenotype linked to matrix metalloproteinase-9 gelatinase expression","volume":"78","author":"Llorens","year":"1998","journal-title":"Lab. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1159\/000101319","article-title":"Signaling pathways involved in collagen-induced disruption of the E-cadherin complex during epithelial-mesenchymal transition","volume":"185","author":"Imamichi","year":"2007","journal-title":"Cells Tissues Organs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1091\/mbc.e07-03-0249","article-title":"Differential Regulation of Epithelial and Mesenchymal Markers by \u03b4EF1 Proteins in Epithelial\u2013Mesenchymal Transition Induced by TGF-\u03b2","volume":"18","author":"Shirakihara","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"964","DOI":"10.7150\/ijbs.4564","article-title":"Complexities of TGF-\u03b2 targeted cancer therapy","volume":"8","author":"Connolly","year":"2012","journal-title":"Int. J. Biol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","article-title":"TGF\u03b2 in Cancer","volume":"134","year":"2008","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ccr.2009.02.011","article-title":"TGF-\u03b2 increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma","volume":"15","author":"Anido","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ccr.2014.03.010","article-title":"A long noncoding RNA activated by TGF-\u03b2 promotes the invasion-metastasis cascade in hepatocellular carcinoma","volume":"25","author":"Yuan","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1158\/0008-5472.CAN-12-0299","article-title":"CD44s regulates the TGF-\u03b2-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma","volume":"72","author":"Mima","year":"2012","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21113","DOI":"10.1074\/jbc.M211304200","article-title":"Transforming growth factor \u03b2-1 induces snail transcription factor in epithelial cell lines: Mechanisms for epithelial mesenchymal transitions","volume":"278","author":"Peinado","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/nrm2297","article-title":"TGF\u03b2-SMAD signal transduction: Molecular specificity and functional flexibility","volume":"8","author":"Schmierer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1083\/jcb.200512110","article-title":"Transforming growth factor-\u03b2 employs HMGA2 to elicit epithelial-mesenchymal transition","volume":"174","author":"Thuault","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1158\/0008-5472.CAN-06-1680","article-title":"Smad4 Regulates Claudin-1 Expression in a Transforming Growth Factor-\u03b2\u2013Independent Manner in Colon Cancer Cells","volume":"67","author":"Shiou","year":"2007","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10735-018-9763-6","article-title":"Smad4 and epithelial-mesenchymal transition proteins in colorectal carcinoma: An immunohistochemical study","volume":"49","author":"Ioannou","year":"2018","journal-title":"J. Mol. Histol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrm1835","article-title":"Complex networks orchestrate epithelial-mesenchymal transitions","volume":"7","author":"Thiery","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1126\/science.1105718","article-title":"Regulation of the polarity protein Par6 by TGF\u03b2 receptors controls epithelial cell plasticity","volume":"307","author":"Ozdamar","year":"2005","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3957","DOI":"10.1038\/sj.emboj.7601818","article-title":"TGF-\u03b2 activates Erk MAP kinase signalling through direct phosphorylation of ShcA","volume":"26","author":"Lee","year":"2007","journal-title":"EMBO J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/jcb.20458","article-title":"Induction of an epithelial to mesenchymal transition in human immortal and malignant keratinocytes by TGF-\u03b21 involves MAPK, Smad and AP-1 signalling pathways","volume":"95","author":"Davies","year":"2005","journal-title":"J. Cell. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"99205","DOI":"10.18632\/oncotarget.22275","article-title":"TGF\u03b2 activates PI3K-AKT signaling via TRAF6","volume":"8","author":"Song","year":"2017","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/ncb1780","article-title":"The type I TGF-\u03b2 receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner","volume":"10","author":"Sorrentino","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7319","DOI":"10.1073\/pnas.131568898","article-title":"Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis","volume":"98","author":"Bowman","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s13277-015-4374-2","article-title":"MicroRNAs, TGF-\u03b2 signaling, and the inflammatory microenvironment in cancer","volume":"37","author":"Guo","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1158\/1541-7786.MCR-17-0547","article-title":"The long (lncRNA) and short (miRNA) of it: TGF\u03b2-mediated Control of RNA-binding Proteins and non-coding RNAs","volume":"16","author":"Janakiraman","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1091\/mbc.e11-02-0103","article-title":"An autocrine TGF-\u03b2\/ZEB\/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition","volume":"22","author":"Gregory","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1053\/j.gastro.2006.06.016","article-title":"A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer","volume":"131","author":"Spaderna","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/ncb1722","article-title":"The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1","volume":"10","author":"Gregory","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1387\/ijdb.041794hp","article-title":"Transcriptional regulation of cadherins during development and carcinogenesis","volume":"48","author":"Peinado","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41419-020-2254-1","article-title":"The long noncoding RNA TUG1 is required for TGF-\u03b2\/TWIST1\/EMT-mediated metastasis in colorectal cancer cells","volume":"11","author":"Shen","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.canlet.2016.07.015","article-title":"Long non-coding RNA LINC01133 inhibits epithelial\u2013mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6","volume":"380","author":"Kong","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bure, I.V., Nemtsova, M.V., and Zaletaev, D.V. (2019). Roles of E-cadherin and Noncoding RNAs in the Epithelial\u2013mesenchymal Transition and Progression in Gastric Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122870"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/path.1398","article-title":"Role of tissue stroma in cancer cell invasion","volume":"200","author":"Mareel","year":"2003","journal-title":"J. Pathol."},{"key":"ref_67","first-page":"3971","article-title":"TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer cells","volume":"15","author":"Zhou","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1158\/0008-5472.CAN-07-5424","article-title":"TGFBR1*6A enhances the migration and invasion of MCF-7 breast cancer cells through RhoA activation","volume":"68","author":"Rosman","year":"2008","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9837","DOI":"10.1158\/0008-5472.CAN-06-0890","article-title":"Transforming Growth Factor \u03b2 Receptor Type II Inactivation Induces the Malignant Transformation of Intestinal Neoplasms Initiated by Apc Mutation","volume":"66","author":"Upton","year":"2006","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1080\/15384101.2019.1642069","article-title":"Interactions between TGF-\u03b2 type I receptor and hypoxia-inducible factor-\u03b1 mediates a synergistic crosstalk leading to poor prognosis for patients with clear cell renal cell carcinoma","volume":"18","author":"Mallikarjuna","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41419-019-2173-1","article-title":"Sanguinarine inhibits epithelial\u2013mesenchymal transition via targeting HIF-1\u03b1\/TGF-\u03b2 feed-forward loop in hepatocellular carcinoma","volume":"10","author":"Su","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"765","DOI":"10.2174\/1871520622666220831124321","article-title":"Molecular Mechanisms of Sanguinarine in Cancer Prevention and Treatment","volume":"23","author":"Ullah","year":"2023","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"153500","DOI":"10.1016\/j.phymed.2021.153500","article-title":"Sanguinarine impedes metastasis and causes inversion of epithelial to mesenchymal transition in breast cancer","volume":"84","author":"Ghauri","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"100422","DOI":"10.1016\/j.ctarc.2021.100422","article-title":"Tumor angiogenesis: Current challenges and therapeutic opportunities","volume":"28","author":"Salah","year":"2021","journal-title":"Cancer Treat Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2147\/vhrm.2006.2.3.213","article-title":"Angiogenesis in cancer","volume":"2","author":"Nishida","year":"2006","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_76","first-page":"S44","article-title":"TGF-\u03b2 signaling in cancer\u2014A double-edged sword","volume":"11","author":"Akhurst","year":"2001","journal-title":"Trends Cell Biol."},{"key":"ref_77","first-page":"699","article-title":"TGF-\u03b2 signaling: A complex role in tumorigenesis","volume":"17","author":"Liu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Seoane, J., and Gomis, R.R. (2017). TGF-\u03b2 Family Signaling in Tumor Suppression and Cancer Progression. Cold Spring Harb. Perspect. Biol, 9.","DOI":"10.1101\/cshperspect.a022277"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1074\/jbc.M002016200","article-title":"Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2)","volume":"276","author":"Gille","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_80","first-page":"29","article-title":"Vascular endothelial growth factor: An important molecular target of curcumin","volume":"59","author":"Katsiki","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.7150\/thno.51507","article-title":"Metastatic colorectal cancer cells maintain the TGF\u03b2 program and use TGFBI to fuel angiogenesis","volume":"11","author":"Chiavarina","year":"2021","journal-title":"Theranostics"},{"key":"ref_82","first-page":"21","article-title":"Actions of TGF-\u03b2 as tumor suppressor and pro-metastatic factor in human cancer","volume":"1775","author":"Pardali","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.tcb.2010.06.006","article-title":"Signaling by members of the TGF-\u03b2 family in vascular morphogenesis and disease","volume":"20","author":"Pardali","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.18632\/oncotarget.14283","article-title":"PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1\/Twist1 pathway","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"38527","DOI":"10.1074\/jbc.M104536200","article-title":"Synergistic cooperation between hypoxia and transforming growth factor-\u03b2 pathways on human vascular endothelial growth factor gene expression","volume":"276","author":"Botella","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Rada, M., Kapelanski-Lamoureux, A., Petrillo, S., Tabari\u00e8s, S., Siegel, P., Reynolds, A.R., Lazaris, A., and Metrakos, P. (2021). Runt related transcription factor-1 plays a central role in vessel co-option of colorectal cancer liver metastases. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02481-8"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9624","DOI":"10.1073\/pnas.97.17.9624","article-title":"Smad4\/DPC4-mediated tumor suppression through suppression of angiogenesis","volume":"97","author":"Volpert","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1038\/nature25492","article-title":"TGF\u03b2 drives immune evasion in genetically reconstituted colon cancer metastasis","volume":"554","author":"Tauriello","year":"2018","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1038\/s41388-021-01713-9","article-title":"ZNF37A promotes tumor metastasis through transcriptional control of THSD4\/TGF-\u03b2 axis in colorectal cancer","volume":"40","author":"Liu","year":"2021","journal-title":"Oncogene"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Peng, C., Zou, X., Xia, W., Gao, H., Li, Z., Liu, N., Xu, Z., Gao, C., He, Z., and Niu, W. (2018). Integrin \u03b1v\u03b26 plays a bi-directional regulation role between colon cancer cells and cancer-associated fibroblasts. Biosci. Rep., 38.","DOI":"10.1042\/BSR20180243"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.ccr.2012.08.013","article-title":"Dependency of Colorectal Cancer on a TGF-\u03b2-Driven Program in Stromal Cells for Metastasis Initiation","volume":"22","author":"Calon","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00441-014-2075-6","article-title":"Co-migration of colon cancer cells and CAFs induced by TGF\u03b21 enhances liver metastasis","volume":"359","author":"Dotor","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.canlet.2020.07.023","article-title":"Cancer-associated fibroblasts-derived exosomal miR-17-5p promotes colorectal cancer aggressive phenotype by initiating a RUNX3\/MYC\/TGF-\u03b21 positive feedback loop","volume":"491","author":"Zhang","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1074\/jbc.M109.076919","article-title":"ADAMTSL-6 is a novel extracellular matrix protein that binds to fibrillin-1 and promotes fibrillin-1 fibril formation","volume":"285","author":"Tsutsui","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"38602","DOI":"10.1074\/jbc.M111.243451","article-title":"ADAMTSL6\u03b2 Protein Rescues Fibrillin-1 Microfibril Disorder in a Marfan Syndrome Mouse Model through the Promotion of Fibrillin-1 Assembly","volume":"286","author":"Saito","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2368249","DOI":"10.1155\/2019\/2368249","article-title":"Tumour-Associated Macrophages (TAMs) in Colon Cancer and How to Reeducate Them","volume":"2019","author":"Yahaya","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_97","first-page":"133","article-title":"The role of tumor-associated macrophage in breast cancer biology","volume":"33","author":"Choi","year":"2018","journal-title":"Histol. Histopathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.canlet.2019.05.019","article-title":"Individualized precision treatment: Targeting TAM in HCC","volume":"458","author":"Li","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1111\/cas.15101","article-title":"Tumor-associated macrophage-derived transforming growth factor-\u03b2 promotes colorectal cancer progression through HIF1-TRIB3 signaling","volume":"112","author":"Liu","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1002\/jcp.29317","article-title":"c-Fos separation from Lamin A\/C by GDF15 promotes colon cancer invasion and metastasis in inflammatory microenvironment","volume":"235","author":"Ding","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"215795","DOI":"10.1016\/j.canlet.2022.215795","article-title":"Dual inhibition of TGF\u03b2 signaling and CSF1\/CSF1R reprograms tumor-infiltrating macrophages and improves response to chemotherapy via suppressing PD-L1","volume":"543","author":"Chen","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.1038\/s41388-021-01827-0","article-title":"CTHRC1 promotes liver metastasis by reshaping infiltrated macrophages through physical interactions with TGF-\u03b2 receptors in colorectal cancer","volume":"40","author":"Zhang","year":"2021","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.2147\/OTT.S336548","article-title":"M2-Type Macrophages Induce Tregs Generation by Activating the TGF-\u03b2\/Smad Signalling Pathway to Promote Colorectal Cancer Development","volume":"14","author":"Ma","year":"2021","journal-title":"OncoTarg. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ccell.2019.08.003","article-title":"Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis","volume":"36","author":"Jackstadt","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12307-017-0198-5","article-title":"Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer","volume":"10","author":"Miteva","year":"2017","journal-title":"Cancer Microenviron."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Lee, H., Kong, J.S., Lee, S.S., and Kim, A. (2021). Radiation-Induced Overexpression of TGF\u03b2 and PODXL Contributes to Colorectal Cancer Cell Radioresistance through Enhanced Motility. Cells, 10.","DOI":"10.3390\/cells10082087"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41556-017-0027-6","article-title":"Tumour spheres with inverted polarity drive the formation of peritoneal metastases in patients with hypermethylated colorectal carcinomas","volume":"20","author":"Zajac","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Shima, K., Morikawa, T., Yamauchi, M., Kuchiba, A., Imamura, Y., Liao, X., Meyerhardt, J.A., Fuchs, C.S., and Ogino, S. (2011). TGFBR2 and BAX Mononucleotide Tract Mutations, Microsatellite Instability, and Prognosis in 1072 Colorectal Cancers. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025062"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1158\/0008-5472.CAN-17-3303","article-title":"Combined Mutation of Apc, Kras, and Tgfbr2 Effectively Drives Metastasis of Intestinal Cancer","volume":"78","author":"Sakai","year":"2018","journal-title":"Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1053\/gast.2003.50094","article-title":"Pathology of mouse models of intestinal cancer: Consensus report and recommendations","volume":"124","author":"Boivin","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Bajenova, O., Gorbunova, A., Evsyukov, I., Rayko, M., Gapon, S., Bozhokina, E., Shishkin, A., and O\u2019Brien, S.J. (2016). The Genome-Wide Analysis of Carcinoembryonic Antigen Signaling by Colorectal Cancer Cells Using RNA Sequencing. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161256"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1200\/JCO.2021.39.15_suppl.2510","article-title":"Safety, pharmacokinetic and pharmacodynamic results from dose escalation of SAR439459, a TGF\u03b2 inhibitor, as monotherapy or in combination with cemiplimab in a phase 1\/1b study","volume":"39","author":"Williamson","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e1811605","DOI":"10.1080\/2162402X.2020.1811605","article-title":"Pan-TGF\u03b2 inhibition by SAR439459 relieves immunosuppression and improves antitumor efficacy of PD-1 blockade","volume":"9","author":"Greco","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1007\/s00280-019-03916-0","article-title":"A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial)","volume":"84","author":"Clarke","year":"2019","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1200\/JCO.2018.36.4_suppl.764","article-title":"M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-\u03b2, in patients with heavily pretreated CRC: Preliminary results from a phase I trial","volume":"36","author":"Kopetz","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1158\/2767-9764.CRC-22-0194","article-title":"Bintrafusp alfa, an anti-PD-L1:TGF-\u03b2 trap fusion protein, in patients with ctDNA-positive, liver-limited metastatic colorectal cancer","volume":"2","author":"Morris","year":"2022","journal-title":"Cancer Res. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1200\/JCO.2021.39.3_suppl.79","article-title":"Phase II trial of bintrafusp alfa in patients with metastatic MSI-H cancers following progression on immunotherapy","volume":"39","author":"Morris","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e007353","DOI":"10.1136\/jitc-2023-007353","article-title":"Phase I\/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-\u03b2 monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors","volume":"11","author":"Bauer","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e005267","DOI":"10.1136\/jitc-2022-005267","article-title":"Phase 1 first-in-human study of dalutrafusp alfa, an anti-CD73-TGF-\u03b2-trap bifunctional antibody, in patients with advanced solid tumors","volume":"11","author":"Tolcher","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/carcin\/bgaa142","article-title":"A novel approach for monitoring TGF-\u03b2 signaling in vivo in colon cancer","volume":"42","author":"Zhang","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Otegbeye, F., Ojo, E., Moreton, S., Mackowski, N., Lee, D.A., De Lima, M., and Wald, D.N. (2018). Inhibiting TGF-\u03b2 signaling preserves the function of highly activated, in vitro expanded natural killer cells in AML and colon cancer models. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191358"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12032-021-01464-3","article-title":"Dual inhibition of TGF\u03b2 and AXL as a novel therapy for human colorectal adenocarcinoma with mesenchymal phenotype","volume":"38","author":"Ciardiello","year":"2021","journal-title":"Med. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"301","DOI":"10.2144\/000114037","article-title":"Visiting \u201cNoncodarnia\u201d","volume":"54","author":"Perkel","year":"2013","journal-title":"Biotechniques"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.tips.2022.01.008","article-title":"The potential of long noncoding RNA therapies","volume":"43","author":"Mercer","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"143960","DOI":"10.1016\/j.gene.2019.143960","article-title":"LncRNA MIR503HG is downregulated in Han Chinese with colorectal cancer and inhibits cell migration and invasion mediated by TGF-\u03b22","volume":"713","author":"Chuo","year":"2019","journal-title":"Gene"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Liu, Z., Wang, N., Wang, F., Zhang, S., and Ding, J. (2019). Silencing of lncRNA EZR-AS1 inhibits proliferation, invasion, and migration of colorectal cancer cells through blocking transforming growth factor \u03b2 signaling. Biosci. Rep., 39.","DOI":"10.1042\/BSR20191199"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41418-020-0596-y","article-title":"LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-\u03b2\/SMAD2\/3 signaling pathway","volume":"28","author":"Wu","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/iub.2454","article-title":"The mechanism of sitagliptin inhibition of colorectal cancer cell lines\u2019 metastatic functionalities","volume":"73","author":"Carvalho","year":"2021","journal-title":"IUBMB Life"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.18632\/oncotarget.9830","article-title":"Loss of TGF\u03b2 signaling promotes colon cancer progression and tumor-associated inflammation","volume":"8","author":"Principe","year":"2016","journal-title":"Oncotarget"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s00280-017-3245-5","article-title":"A phase 1 study of anti-TGF\u03b2 receptor type-II monoclonal antibody LY3022859 in patients with advanced solid tumors","volume":"79","author":"Tolcher","year":"2017","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.5754\/hge11186","article-title":"Smad4 may help to identify a subset of colorectal cancer patients with early recurrence after curative therapy","volume":"58","author":"Ahn","year":"2011","journal-title":"Hepatogastroenterology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1158\/1078-0432.CCR-04-1458","article-title":"SMAD4 as a prognostic marker in colorectal cancer","volume":"11","author":"Alazzouzi","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1200\/JCO.2005.01.086","article-title":"Systematic review of microsatellite instability and colorectal cancer prognosis","volume":"23","author":"Popat","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s12038-016-9624-y","article-title":"Therapeutic resistance and cancer recurrence mechanisms: Unfolding the story of tumour coming back","volume":"41","author":"Esmatabadi","year":"2016","journal-title":"J. Biosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"E5990","DOI":"10.1073\/pnas.1801348115","article-title":"Hypoxic tumor microenvironment activates GLI2 via HIF-1\u03b1 and TGF-\u03b22 to promote chemoresistance in colorectal cancer","volume":"115","author":"Tang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3892\/ol.2017.6209","article-title":"Transforming growth factor-\u03b21 contributes to oxaliplatin resistance in colorectal cancer via epithelial to mesenchymal transition","volume":"14","author":"Mao","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"22077","DOI":"10.18632\/oncotarget.7895","article-title":"The TGF-\u03b2 pathway is activated by 5-fluorouracil treatment in drug resistant colorectal carcinoma cells","volume":"7","author":"Romano","year":"2016","journal-title":"Oncotarget"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"294097","DOI":"10.1155\/2012\/294097","article-title":"Crosstalk between p53 and TGF-\u03b2 Signalling","volume":"2012","author":"Elston","year":"2012","journal-title":"J. Signal Transduct."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41389-020-0228-x","article-title":"Loss of HAT1 expression confers BRAFV600E inhibitor resistance to melanoma cells by activating MAPK signaling via IGF1R","volume":"9","author":"Bugide","year":"2020","journal-title":"Oncogenesis"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1080\/03007995.2016.1211522","article-title":"The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: From rash mitigation to the increase in anti-tumor activity","volume":"32","author":"Boccellino","year":"2016","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature13121","article-title":"Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma","volume":"508","author":"Sun","year":"2014","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/pcmr.12578","article-title":"MicroRNA-125a promotes resistance to BRAF inhibitors through suppression of the intrinsic apoptotic pathway","volume":"30","author":"Hanniford","year":"2017","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"81995","DOI":"10.18632\/oncotarget.13226","article-title":"Mutational activation of BRAF confers sensitivity to transforming growth factor \u03b2 inhibitors in human cancer cells","volume":"7","author":"Spender","year":"2016","journal-title":"Oncotarget"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.1158\/1078-0432.CCR-13-0423","article-title":"Increased TGF-\u03b1 as a mechanism of acquired resistance to the anti-EGFR inhibitor cetuximab through EGFR-MET interaction and activation of MET signaling in colon cancer cells","volume":"19","author":"Troiani","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/S1470-2045(22)00446-6","article-title":"Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: A single-arm, phase 2 trial","volume":"23","author":"Yamazaki","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/mc.23373","article-title":"Setting up clinical trials for success: Applying preclinical advances in combined TGF\u03b2\/PD-L1 inhibition to ongoing clinical studies","volume":"61","author":"Strait","year":"2022","journal-title":"Mol. Carcinog."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:10:50Z","timestamp":1760109050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":146,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137400"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137400","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]}}}