{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:25:26Z","timestamp":1791923126541,"version":"4.3.4"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["No. 2019R1A2C1008984"],"award-info":[{"award-number":["No. 2019R1A2C1008984"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["No. 2019R1A2C1008984"],"award-info":[{"award-number":["No. 2019R1A2C1008984"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Resistance to 5-fluorouracil (5-FU) and oxaliplatin (OXA) remains an obstacle in colorectal cancer (CRC) therapy, but the upstream mechanisms enabling adaptive survival remain unclear. Angiomotin (AMOT), a Hippo-YAP regulator, is expressed as two major isoforms, p130 and p80, but the contribution of isoform-specific AMOT regulation to chemoresistance is unknown. RNA-seq of OXA-resistant cells identified AMOT as a candidate determinant, and its isoform-specific regulation and functional relevance were then examined in OXA- and 5-FU-resistant CRC sublines. AMOT-p80 was preferentially upregulated, whereas AMOT-p130 remained largely unchanged. Common AMOT pre-mRNA was elevated, whereas p130-specific pre-mRNA was unchanged, consistent with preferential transcriptional activation favoring the p80 isoform. Functionally, AMOT depletion minimally affected basal viability but significantly sensitized resistant cells to 5-FU or OXA, with increased apoptotic responses. AMOT silencing reduced nuclear YAP and lowered c-Myc and Cyclin D1 protein levels, whereas AMOT-p80 re-expression restored nuclear YAP, with recovery of c-Myc\/Cyclin D1 levels and drug tolerance. YAP knockdown attenuated these outputs and blunted the additional effect of AMOT depletion. AMOT-p80 overexpression in parental cells increased c-Myc\/Cyclin D1 protein levels and enhanced tolerance to 5-FU and OXA. These findings suggest that preferential AMOT-p80 upregulation is linked to YAP-associated chemoresistant phenotypes in CRC cells.<\/jats:p>","DOI":"10.3390\/biom16060767","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:08Z","timestamp":1779465968000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Preferential Upregulation of AMOT-p80 Is Associated with YAP-Linked Resistance to 5-Fluorouracil and Oxaliplatin in Colorectal Cancer Cells"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1976-7750","authenticated-orcid":false,"given":"Yeho","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1302-9462","authenticated-orcid":false,"given":"Jin-Kyung","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Yeom","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2755-6010","authenticated-orcid":false,"given":"Jae-Hyeon","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-4589","authenticated-orcid":false,"given":"Joo-Ho","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyung","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-2279","authenticated-orcid":false,"given":"Yunjong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Yun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Azwar, S., Seow, H.F., Abdullah, M., Faisal Jabar, M., and Mohtarrudin, N. (2021). Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment. Biology, 10.","DOI":"10.3390\/biology10090854"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.7150\/thno.69424","article-title":"Platinum-based drugs for cancer therapy and anti-tumor strategies","volume":"12","author":"Zhang","year":"2022","journal-title":"Theranostics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1042\/CS20201474","article-title":"The Hippo pathway in cancer: YAP\/TAZ and TEAD as therapeutic targets in cancer","volume":"136","author":"Cunningham","year":"2022","journal-title":"Clin. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mokhtari, R.B., Ashayeri, N., Baghaie, L., Sambi, M., Satari, K., Baluch, N., Bosykh, D.A., Szewczuk, M.R., and Chakraborty, S. (2023). The Hippo Pathway Effectors YAP\/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment. Cancers, 15.","DOI":"10.3390\/cancers15133468"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Sheldon, M., Sun, Y., and Ma, L. (2023). New Insights into YAP\/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer. Cancers, 15.","DOI":"10.3390\/cancers15235497"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5767535","DOI":"10.1155\/2024\/5767535","article-title":"Hippo Signaling Pathway in Colorectal Cancer: Modulation by Various Signals and Therapeutic Potential","volume":"2024","author":"Mohammadpour","year":"2024","journal-title":"Anal. Cell. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Mouillet-Richard, S., and Laurent-Puig, P. (2020). YAP\/TAZ Signalling in Colorectal Cancer: Lessons from Consensus Molecular Subtypes. Cancers, 12.","DOI":"10.3390\/cancers12113160"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6784","DOI":"10.7150\/jca.100179","article-title":"YAP Promotes Chemoresistance to 5-FU in Colorectal Cancer Through mTOR\/GLUT3 Axis","volume":"15","author":"Xu","year":"2024","journal-title":"J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e23966","DOI":"10.7554\/eLife.23966","article-title":"Regulation of localization and function of the transcriptional co-activator YAP by angiomotin","volume":"6","author":"Moleirinho","year":"2017","journal-title":"eLife"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1101\/gad.2000111","article-title":"Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein","volume":"25","author":"Zhao","year":"2011","journal-title":"Genes Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1111\/j.1742-4658.2006.05216.x","article-title":"p130-angiomotin associates to actin and controls endothelial cell shape","volume":"273","author":"Ernkvist","year":"2006","journal-title":"FEBS J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1158\/0008-5472.CAN-10-1995","article-title":"The adaptor protein AMOT promotes the proliferation of mammary epithelial cells via the prolonged activation of the extracellular signal-regulated kinases","volume":"71","author":"Ranahan","year":"2011","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1038\/onc.2014.333","article-title":"Angiomotin decreases lung cancer progression by sequestering oncogenic YAP\/TAZ and decreasing Cyr61 expression","volume":"34","author":"Hsu","year":"2015","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12967-018-1466-y","article-title":"The physiological role of Motin family and its dysregulation in tumorigenesis","volume":"16","author":"Huang","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ra77","DOI":"10.1126\/scisignal.2004060","article-title":"The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis","volume":"6","author":"Yi","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1091\/mbc.e13-11-0701","article-title":"Angiomotins link F-actin architecture to Hippo pathway signaling","volume":"25","author":"Paramasivam","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10145","DOI":"10.18632\/oncotarget.14358","article-title":"Angiomotin regulates prostate cancer cell proliferation by signaling through the Hippo-YAP pathway","volume":"8","author":"Zeng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1742-7843.2007.00115.x","article-title":"Effect of betulinic acid on anticancer drug-resistant colon cancer cells","volume":"101","author":"Jung","year":"2007","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41401-020-00539-7","article-title":"A brief guide to good practices in pharmacological experiments: Western blotting","volume":"42","author":"Tie","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_20","first-page":"701","article-title":"YAP promotes epithelial mesenchymal transition by upregulating Slug expression in human colorectal cancer cells","volume":"13","author":"Cheng","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10498","DOI":"10.1038\/ncomms10498","article-title":"ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types","volume":"7","author":"Lehmann","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.3892\/or.2016.5194","article-title":"Angiomotin promotes the malignant potential of colon cancer cells by activating the YAP-ERK\/PI3K-AKT signaling pathway","volume":"36","author":"Zhang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/ncb3216","article-title":"Genome-wide association between YAP\/TAZ\/TEAD and AP-1 at enhancers drives oncogenic growth","volume":"17","author":"Zanconato","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.stemcr.2019.03.009","article-title":"Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells","volume":"12","author":"Zaltsman","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.1074\/jbc.C110.212621","article-title":"Hippo pathway-independent restriction of TAZ and YAP by angiomotin","volume":"286","author":"Chan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2400076","DOI":"10.1002\/bies.202400076","article-title":"Angiomotin family proteins in the Hippo signaling pathway","volume":"46","author":"Wang","year":"2024","journal-title":"BioEssays"},{"key":"ref_27","first-page":"483","article-title":"The Hippo\/YAP signaling pathway: The driver of cancer metastasis","volume":"20","author":"Zhou","year":"2023","journal-title":"Cancer Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the roots of cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"50333","DOI":"10.18632\/oncotarget.10385","article-title":"5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-\u03b2-synthase in colon cancer cells lacking p53","volume":"7","author":"Pagliara","year":"2016","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jprot.2017.05.005","article-title":"Proteomic profiling reveals DNA damage, nucleolar and ribosomal stress are the main responses to oxaliplatin in cancer cells","volume":"162","author":"Ozdian","year":"2017","journal-title":"J. Proteom."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Carotenuto, P., Pecoraro, A., Palma, G., Russo, G., and Russo, A. (2019). Therapeutic approaches targeting nucleolus in cancer. Cells, 8.","DOI":"10.3390\/cells8091090"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.chembiol.2023.06.010","article-title":"Inhibition of nucleolar transcription by oxaliplatin involves ATM\/ATR kinase signaling","volume":"30","author":"Nechay","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4143\/crt.2005.37.1.1","article-title":"Biology of SNU cell lines","volume":"37","author":"Ku","year":"2005","journal-title":"Cancer Res. Treat."},{"key":"ref_34","first-page":"183","article-title":"p53 functional loss in a colon cancer cell line with two missense mutations (218leu and 248trp) on separate alleles","volume":"98","author":"Rand","year":"1996","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Voutsadakis, I.A. (2022). Sensitivities and dependencies of BRAF mutant colorectal cancer cell lines with or without PIK3CA mutations for discovery of vulnerabilities with therapeutic potential. Medicina, 58.","DOI":"10.3390\/medicina58101498"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/767\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:23:01Z","timestamp":1779466981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/6\/767"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biom16060767"],"URL":"https:\/\/doi.org\/10.3390\/biom16060767","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}