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Updated: Aug 7, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
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The TRPM7 channel reprograms cellular glycolysis to drive tumorigenesis and angiogenesis

Wanzhou Wu1,2,3, Xuan Wang3, Longsheng Liao3

  • 1Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China.

Cell Death & Disease
|March 6, 2023
PubMed

Insights

The TRPM7 ion channel controls cellular glycolysis, impacting cancer growth and blood vessel formation. Inhibiting TRPM7-dependent glycolysis offers a potential strategy for cancer therapy.

Area of Science:

  • Cellular metabolism
  • Ion channel function
  • Cancer biology

Background:

  • Cancer and endothelial cells preferentially use aerobic glycolysis for energy.
  • Intracellular ionic signaling regulates glucose metabolism, but the specific ion channel involved remains unknown.
  • Identifying regulators of cellular glycolysis is crucial for understanding cancer progression.

Purpose of the Study:

  • To identify the ion channel regulating cellular glycolysis.
  • To elucidate the molecular mechanisms by which this channel controls glucose metabolism.
  • To evaluate the therapeutic potential of targeting this channel in cancer.

Main Methods:

  • RNA sequencing (RNA-seq) to analyze gene expression.
  • Metabolomics to study metabolic pathways.
  • Genetic assays to determine gene function.
  • Xenograft tumor models in mice.
  • Retinal angiogenesis assays in mice.

Main Results:

  • The Transient Receptor Potential Melastatin 7 (TRPM7) channel was identified as a regulator of cellular glycolysis.
  • TRPM7 deletion suppressed cancer cell glycolysis and reduced tumor burden.
  • Endothelial TRPM7 deficiency inhibited postnatal retinal angiogenesis.
  • TRPM7 regulates the expression of solute carrier family 2 member 3 (SLC2A3/GLUT3) via calcium influx, calcineurin, and CREB/CRTC2 signaling.
  • Restoring CRTC2 or CREB activity in TRPM7-deficient cells normalized glycolysis and cell growth.

Conclusions:

  • TRPM7 is a novel regulator of glycolytic reprogramming in cancer and endothelial cells.
  • The TRPM7-SLC2A3/GLUT3 axis represents a new signaling pathway controlling glucose metabolism.
  • Targeting TRPM7-dependent glycolysis presents a promising avenue for cancer therapy.

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