4.7 Article

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

Journal

CANCER LETTERS
Volume 525, Issue -, Pages 55-66

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.09.027

Keywords

Colorectal cancer; p53; MDM2

Categories

Funding

  1. Key R&D Program of Sichuan Province, China [2021YFS0224]
  2. Basic Research for Application of Sichuan Province, China [2020YJ0066]
  3. Fund of the High Quality Development of Guang'an People's Hospital [21FZ008]
  4. 1.3.5 project for disciplines of excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University [19HXFH054]
  5. 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYGD20003, ZYJC18034]
  6. National Natural Science Foundation of China [81572931]

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The study reveals the expression and function of SLC5 family members in colorectal cancer, showing that downregulation of SLC5A7 correlates with CRC staging and prognosis response. Overexpression of SLC5A7 inhibits CRC growth by promoting p53 protein expression, suggesting a potential therapeutic target for CRC.
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.

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