Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Exploratory Proteomic Profiling Reveals Potential Mediators of 5-FU Response under p53 Deficiency in Colon Cancer Cells

  • Seonyong Lee (College of Pharmacy, Duksung Women's University) ;
  • Jiwon Lee (College of Pharmacy, Duksung Women's University) ;
  • Ga Seul Lee (Core Research Facility & Analysis Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Jeong Hee Moon (Core Research Facility & Analysis Center, Korea Research Institute of Bioscience & Biotechnology) ;
  • Joohee Jung (College of Pharmacy, Duksung Women's University)
  • Received : 2024.12.06
  • Accepted : 2025.12.15
  • Published : 2026.03.01
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Abstract

Mutations in p53 have been implicated in poor prognosis and reduced sensitivity to 5-fluorouracil (5-FU) treatment in colon cancer. While p53-dependent mechanisms have been widely studies, less is known about how p53 deficiency reshapes cellular signaling and contributes to 5-FU resistance. In this study, we aimed to profile proteomic alterations associated with p53 loss by comparing colon cancer cells with and without p53 expression. Differentially expressed proteins (DEPs) related to cell cycle regulation were of particular interest, as 5-FU treatment induced G1 phase arrest in HCT116 p53 wild-type (WT) cells, whereas p53 knockout (KO) cells predominantly showed S phase arrest. We identified several DEPs in p53 deficient cells following 5-FU treatment. Notably, F3 expression was increased, while aldehyde dehydrogenase family 1 member A4 (ALDH1A3), histone deacetylase 2 (HDAC2), and protein S100-A4 (S100A4) were decreased. The expression levels of these genes were associated with overall survival in patients with colon cancer. These findings highlight proteomic alterations linked to p53 deficiency and support a proposed model in which differential regulation of specific proteins may be associated with reduced sensitivity to 5-FU, providing a basis for future mechanistic and functional studies.

Keywords

Acknowledgement

We would like to thank Editage (www.editage.co.kr) for English language editing. This research was supported by an NRF grant from the MSIT (NRF-2021R1A2C2004535).

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