TRPC1/3/6 inhibition attenuates the TGF‐β1‐induced epithelial–mesenchymal transition in gastric cancer via the Ras/Raf1/ERK signaling pathway. (10th May 2018)

• Record Type: Journal Article
• Authors: Ge, Pengbo; Wei, Linting; Zhang, Mingkai; Hu, Baoguang; Wang, Kai; Li, Yanbin; Liu, Shuaichen; Wang, Jianping; Li, Yuming
• Is Part Of: Cell biology international. Volume 42:Number 8(2018)
• Page Start: 975
• Page End: 984
• Publication Date: 2018-05-10
• Subjects: epithelial–mesenchymal transition -- gastric cancer -- TGF‐β1 -- TRPC; Cytology -- Periodicals; Cells -- Periodicals; 571.605
• DOI: 10.1002/cbin.10963
• Languages: English
• ISSNs: 1065-6995

Abstract

Abstract: Gastric cancer (GC) is one of the most common malignancies worldwide. TGF‐β1 induces the epithelial–mesenchymal transition (EMT) in GC, mainly through Smad‐dependent pathways. Nevertheless, few studies have focused on the activation of non‐canonical transduction pathways. TRPC, Ca 2+ entry channels, are ubiquitously expressed in various cell types and are involved in many cellular functions. However, their roles in GC are not well elucidated. This study aimed to determine whether TRPC participates in the TGF‐β1‐induced EMT of GC and to investigate the potential mechanisms. Immunofluorescence staining was performed to examine the distribution and expression of TRPCs and EMT‐related proteins in SGC‐7901 cells incubated with or without TGF‐β1. The expression of TRPC1/3/6 and EMT‐related molecules, including E‐cadherin, vimentin, and α‐SMA, was detected by qRT‐PCR and Western blotting. Additionally, the underlying mechanism was determined by treating cells with pharmacological inhibitors and examining the levels of proteins involved in the main signaling cascades using Western blotting. TRPC1/3/6 were expressed at high levels in SGC‐7901 cells. Following TGF‐β1 stimulation, the expression of vimentin, α‐SMA, and TRPC1/3/6 increased and E‐cadherin expression decreased, accompanied by activation of the Ras/Raf1/ERK1/2 signaling pathway. Notably, activation of the Ras/Raf1/ERK1/2 signaling cascade was suppressed by SKF96365 and 2‐APB. Both TRPC and ERK inhibitors mitigated EMT progression. Based on these results, TRPC1/3/6 inhibition attenuated the TGF‐β1‐induced EMT in GC by suppressing Ras/Raf1/ERK signal transduction.