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TMEM206 Contributes to Cancer Hallmark Functions in Colorectal Cancer Cells and Is Regulated by p53 in a
Korollus Melek1, Barbara Hauert1, Sven Kappel1
1Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
Cells
|November 27, 2024
Summary
The tumor suppressor p53 regulates TMEM206, a protein involved in acid-induced ion flux. In colorectal cancer, TMEM206 promotes cancer hallmarks and its expression is controlled by p53 via p21.
Area of Science:
- Molecular Biology
- Cancer Biology
- Ion Channel Physiology
Background:
- Acid-induced ion flux is implicated in pathologies like cancer.
- TMEM206 was identified as the molecular component of acid-induced chloride flux.
- The tumor suppressor p53 is frequently mutated in human cancers.
Purpose of the Study:
- To investigate the regulation of TMEM206 by p53.
- To determine TMEM206's role in colorectal cancer (CRC) hallmark functions.
- To elucidate TMEM206's contribution to acid-induced cell death in CRC cells.
Main Methods:
- Generated p53-deficient HCT116 colorectal cancer cells.
- Assessed TMEM206-mediated chloride currents using patch-clamp.
- Utilized dual-luciferase reporter assays for transcriptional regulation analysis.
- Performed migration, metabolic activity, and cell death assays.
Main Results:
- TMEM206 mRNA levels were elevated in human primary CRC tumors.
- TMEM206 knockout increased acid-induced cell death and reduced proliferation/migration.
- p53 deficiency led to increased TMEM206 mRNA and currents, which was rescued by functional p53.
- p21 knockout increased TMEM206 currents, suggesting p21-dependent regulation.
Conclusions:
- TMEM206 is upregulated in colorectal cancer and contributes to cancer hallmark functions.
- TMEM206 expression and function in CRC cells are regulated by p53 through a p21-dependent mechanism.
- TMEM206 represents a potential therapeutic target in p53-mutated colorectal cancers.
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