Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein

Cancer Lett. 2022 Jan 28:525:55-66. doi: 10.1016/j.canlet.2021.09.027. Epub 2021 Sep 22.

Abstract

The members of the solute carrier (SLC) superfamily are vital membrane transporters in human cells. In the present study, we determine the expression and function of SLC5 family members in colorectal cancer (CRC). Expression analysis based on The Cancer Genome Atlas database and potential clinical relation analysis based on the Oncomine database indicate that SLC5A7 is downregulated and is predicted to correlate with the staging, and prognosis response of CRC. Additional results demonstrate that SLC5A7 is downregulated and correlates with good prognosis in patients with CRC. Ectopic expression of SLC5A7 either by overexpression, or uptake of choline efficiently inhibits CRC growth. Examination of the molecular mechanism reveals that SLC5A7 promotes p53 protein expression by directly interacting with and modifying p53 and disrupting the interaction between p53 and MDM2 in wild type p53 CRC cells. Our findings establish the clear correlation between SLC5A7 and tumour growth, providing a novel potential therapeutic target for CRC.

Keywords: Colorectal cancer; MDM2; SLC5A7; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Choline / pharmacology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Protein Interaction Maps / drug effects
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Symporters / genetics*
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • SLC5A7 protein, human
  • Symporters
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Choline