{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T11:54:25Z","timestamp":1774007665826,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yorkshire Cancer Research, UK","award":["B381PA"],"award-info":[{"award-number":["B381PA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>One of the main obstacles to therapeutic success in colorectal cancer (CRC) is the development of acquired resistance to treatment with drugs such as 5-fluorouracil (5-FU). Whilst some resistance mechanisms are well known, it is clear from the stasis in therapy success rate that much is still unknown. Here, a proteomics approach is taken towards identification of candidate proteins using 5-FU-resistant sublines of human CRC cell lines generated in house. Using a multiplexed stable isotope labelling with amino acids in cell culture (SILAC) strategy, 5-FU-resistant and equivalently passaged sensitive cell lines were compared to parent cell lines by growing in Heavy medium with 2D liquid chromatography and Orbitrap Fusion\u2122 Tribrid\u2122 Mass Spectrometry analysis. Among 3003 commonly quantified proteins, six (CD44, APP, NAGLU, CORO7, AGR2, PLSCR1) were found up-regulated, and six (VPS45, RBMS2, RIOK1, RAP1GDS1, POLR3D, CD55) down-regulated. A total of 11 of the 12 proteins have a known association with drug resistance mechanisms or role in CRC oncogenesis. Validation through immunodetection techniques confirmed high expression of CD44 and CD63, two known drug resistance mediators with elevated proteomics expression results. The information revealed by the sensitivity of this method warrants it as an important tool for elaborating the complexity of acquired drug resistance in CRC.<\/jats:p>","DOI":"10.3390\/cells13040342","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T11:18:46Z","timestamp":1707909526000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Proteomic Investigation to Discover Candidate Proteins Involved in Novel Mechanisms of 5-Fluorouracil Resistance in Colorectal Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Mario","family":"Ortega Duran","sequence":"first","affiliation":[{"name":"Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadr ul","family":"Shaheed","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford,  Oxford OX3 9BQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher W.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4647-2340","authenticated-orcid":false,"given":"Steven D.","family":"Shnyder","sequence":"additional","affiliation":[{"name":"Institute of Cancer Therapeutics, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-fluorouracil: Mechanisms of action and clinical strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. 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