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

Yuan Yin1, Zhiyuan Jiang1, Jiamei Fu2

  • 1Department of Gastrointestinal Surgery, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.

Cancer Letters
|September 25, 2021
PubMed

Insights

Solute carrier family 5 member 7 (SLC5A7) is downregulated in colorectal cancer (CRC), correlating with better prognosis. Restoring SLC5A7 inhibits CRC growth by stabilizing p53 protein.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Solute carrier (SLC) superfamily proteins are crucial membrane transporters in human cells.
  • Colorectal cancer (CRC) is a significant global health concern with complex molecular underpinnings.

Purpose of the Study:

  • To investigate the expression and functional role of SLC5 family members in colorectal cancer.
  • To identify potential therapeutic targets for CRC based on SLC transporter activity.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) database for SLC gene expression in CRC.
  • Utilizing the Oncomine database for clinical correlation analysis of SLC5A7.
  • In vitro experiments involving ectopic SLC5A7 expression and choline uptake in CRC cells.
  • Molecular mechanism studies focusing on p53 and MDM2 interactions.

Main Results:

  • SLC5A7 was found to be downregulated in CRC and correlated with improved patient prognosis.
  • Ectopic expression or choline uptake via SLC5A7 significantly inhibited CRC cell growth.
  • SLC5A7 was shown to stabilize p53 protein by disrupting the p53-MDM2 interaction in wild-type p53 CRC cells.

Conclusions:

  • SLC5A7 plays a critical role in regulating colorectal cancer cell growth.
  • The downregulation of SLC5A7 is linked to tumor progression and poorer outcomes.
  • SLC5A7 represents a promising novel therapeutic target for colorectal cancer treatment.
Keywords:
Colorectal cancerMDM2SLC5A7p53

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