Suppression of TRPM7 Inhibited Hypoxia-Induced Migration and Invasion of Androgen-Independent Prostate Cancer Cells

Fei Yang1, Jiarong Cai1, Hailun Zhan1

  • 1Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.

Insights

Transient receptor potential melastatin subfamily member 7 (TRPM7) knockdown inhibits prostate cancer metastasis under hypoxia by promoting HIF-1α degradation. This TRPM7-HIF-1α-Annexin A1 pathway is key to cancer cell migration and invasion.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Prostate cancer metastasis is a significant clinical challenge.
  • The role of Transient Receptor Potential Melastatin subfamily member 7 (TRPM7) in prostate cancer progression, particularly under hypoxia, is not fully understood.
  • Hypoxia is a common feature in solid tumors, promoting aggressive phenotypes.

Purpose of the Study:

  • To investigate the role of TRPM7 in the metastatic ability of androgen-independent prostate cancer cells under hypoxic conditions.
  • To elucidate the molecular mechanisms underlying TRPM7's effect on prostate cancer metastasis in a hypoxic environment.

Main Methods:

  • Data mining to correlate TRPM7 expression with patient survival.
  • Gene knockdown using siRNA, Western blotting, qPCR, luciferase assays, co-immunoprecipitation.
  • Functional assays including wound healing and Transwell assays for cell migration and invasion.

Main Results:

  • High TRPM7 expression correlates with poor prostate cancer patient survival.
  • Hypoxia increases TRPM7 expression and HIF-1α accumulation.
  • TRPM7 knockdown promotes HIF-1α degradation, inhibits EMT, and reduces cell migration/invasion via the HIF-1α-Annexin A1 axis.

Conclusions:

  • TRPM7 knockdown promotes HIF-1α degradation through an oxygen-independent mechanism involving RACK1.
  • The TRPM7-HIF-1α-Annexin A1 signaling axis is critical for hypoxia-induced epithelial-mesenchymal transition (EMT), migration, and invasion in prostate cancer.
  • Targeting TRPM7 may offer a therapeutic strategy for metastatic prostate cancer under hypoxic conditions.

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