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Updated: Nov 2, 2025

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TRPM2 promotes pancreatic cancer by PKC/MAPK pathway

Rui Lin1, Xunxia Bao2,3, Hui Wang4

  • 1General Surgery Department, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. blackchimney@tongji.edu.cn.

Cell Death & Disease
|June 8, 2021
PubMed

Insights

Transient Receptor Potential Melastatin 2 (TRPM2) promotes pancreatic cancer progression by activating the PKC/MAPK pathway. TRPM2 overexpression correlates with poor patient survival and increased tumor stage.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The precise mechanisms driving pancreatic cancer (PA) remain incompletely understood.
  • Previous research indicated a potential role for Transient Receptor Potential Melastatin 2 (TRPM2) in PA.
  • The specific molecular mechanisms by which TRPM2 influences PA progression were yet to be elucidated.

Purpose of the Study:

  • To investigate the role and underlying mechanism of TRPM2 in pancreatic cancer.
  • To establish cellular and animal models for studying TRPM2 function in PA.
  • To correlate TRPM2 expression with clinical outcomes in PA patients.

Main Methods:

  • Construction of pancreatic cancer cell models with TRPM2 overexpression and siRNA.
  • In vitro assays (CCK-8, Transwell, scratch wound) and in vivo nude mice tumor models.
  • Transcriptome analysis, Western blot, PCR, and pathway inhibition studies (PKC/MEK inhibitors).
  • Analysis of clinical data and patient tumor samples.

Main Results:

  • TRPM2 overexpression significantly enhanced proliferation, migration, and invasion in PA cell lines and xenograft models.
  • Elevated TRPM2 levels were negatively correlated with overall and progression-free survival in PA patients.
  • TRPM2 expression increased with advancing tumor stage and was strongly associated with the PKC/MAPK pathway.
  • Inhibition of the PKC/MEK pathway suppressed PA cell proliferation and invasion in TRPM2-overexpressing cells.

Conclusions:

  • TRPM2 plays a critical role in promoting pancreatic cancer progression.
  • TRPM2 activates the downstream MAPK/MEK pathway, potentially via PKC isoforms (PKCα, PKCε, PKCδ).
  • TRPM2 represents a potential therapeutic target for pancreatic cancer.

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