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Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-AM-35
Proteomic Profiling of 5-Fluorouracil Resistance in Colorectal Cancer: Unveiling Molecular Signatures for Targeted Therapy
(1CBDD, Taipei Med. Univ., 2PhD CBDD, Taipei Med. Univ., 3R&D, Natl. Defense Med. Cent., 4GIMS, Natl. Defense Med. Cent.)
oTsui-Chin Huang1,2, Tze-Ting Kuo2,3, Li-Chun Lin2, Hsin-Yi Chang3,4
Colorectal cancer is a leading cause of cancer-related deaths globally. 5-Fluorouracil (5-FU) is a first-line chemotherapy drug that inhibits thymidylate synthase (TYMS), disrupting DNA and RNA synthesis. However, resistance to 5-FU limits its effectiveness. This study investigates the molecular mechanisms of 5-FU resistance and its clinical implications.
We established 5-FU-resistant colorectal cancer cell lines and conducted quantitative proteomics, phosphoproteomics, and plasma membrane proteome analyses. Differentially expressed proteins (DEPs) were validated using shRNA knockdown, qPCR, and western blot. TYMS was significantly upregulated in resistant cells, confirming its role in drug resistance. Enrichment analyses identified dysregulated cell cycle regulation, with CDK1 and CDK2 as key modulators. Notably, RB1 phosphorylation at S807 was observed, potentially affecting its interaction with E2F and leading to increased TYMS expression.
These findings highlight a crucial RB1-E2F-TYMS regulatory axis in 5-FU resistance, suggesting potential therapeutic targets to overcome drug resistance in colorectal cancer.