TRPC3 promotes tumorigenesis of gastric cancer via the CNB2/GSK3β/NFATc2 signaling pathway

Da Cen Lin, Si Yi Zheng, Zhi Guang Zhang, Jian Hua Luo, Zhuang Li Zhu, Li Li, Lu Shan Chen, Xinjian Lin, James S.K. Sham, Mo Jun Lin, Rui Xiang Zhou

Research output: Contribution to journalArticlepeer-review


The transient receptor potential canonical (TRPC) channels have been implicated in various types of malignancies including gastric cancer (GC). However, the detailed mechanisms of TRPC channels underlying cell proliferation and apoptosis of GC cells remain largely unknown. Here, we report that TRPC3 was highly expressed in clinical GC specimens and correlated with GC malignant progression and poor prognosis. Forced expression of TRPC3 in GC cells enhanced both receptor-operated Ca2+ entry (ROCE) and store-operated Ca2+ entry (SOCE) and promoted the nuclear factor of activated T cell 2 (NFATc2) nuclear translocation by AKT/GSK-3β and CNB2 signaling. Pharmacological inhibition of TRPC3 or CRISPR/Cas9-mediated TRPC3 knockout effectively inhibited the growth of GC cells both in vitro and in vivo. These effects were reversible by the rescue of TRPC3 expression. Furthermore, we confirmed the role of TRPC3 and the ROCE-AKT/GSK3β-CNB2/NFATc2 signaling cascade in regulating cell cycle checkpoint, apoptosis cascade, and intracellular ROS production in GC. Overall, our findings suggest an oncogenic role of TRPC3 in GC and may highlight a potential target of TRPC3 for therapeutic intervention of GC and its malignant progression.

Original languageEnglish (US)
Pages (from-to)211-225
Number of pages15
JournalCancer Letters
StatePublished - Oct 28 2021


  • Apoptosis
  • Gastric cancer
  • Nuclear factor of activated T cell 2
  • Proliferation
  • Transient receptor potential canonical 3 channels

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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