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TMEM158 promotes pancreatic cancer aggressiveness by activation of TGFβ1 and PI3K/AKT signaling pathway
Author(s) -
Fu Yue,
Yao Na,
Ding Dong,
Zhang Xudong,
Liu Hanyang,
Ma Le,
Shi Weihai,
Zhu Chunfu,
Tang Liming
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29181
Subject(s) - downregulation and upregulation , pi3k/akt/mtor pathway , cancer research , protein kinase b , signal transduction , pancreatic cancer , cell growth , cancer , cell , tumor progression , epithelial–mesenchymal transition , cell migration , biology , cell cycle , medicine , chemistry , microbiology and biotechnology , metastasis , gene , biochemistry , genetics
Pancreatic cancer (PC) is one of the most deadly digestive cancers world‐wide, with a dismal five‐year survival rate of <8%. Upregulation of transmembrane protein 158 (TMEM158) is known to facilitate the progression of several carcinomas. However, little is known concerning the potential roles of TMEM158 in PC. Herein, we first found that TMEM158 was significantly upregulated in PC samples as well as PC cell lines. The overexpression of TMEM158 was significantly correlated with advanced clinicopathologic features (including tumor size, TNM stage, and blood vessel invasion) and poorer prognosis of patients with PC in clinic. Evidenced based on a series of loss‐ and gain‐of‐function assays uncovered that TMEM158 enhanced PC cell proliferation, migration, and invasion by stimulating the progression of cell cycle, epithelial–mesenchymal transition, and MMP‐2/9 production. Furthermore, mechanism‐related investigations disclosed that activation of TGFβ1 and PI3K/AKT signal might be responsible for TMEM158‐triggered PC aggressiveness. Collectively, TMEM158 was upregulated in PC and promoted PC cell proliferation, migration, and invasion through the activation of TGFβ1 and PI3K/AKT signaling pathways, highlighting its potential as a tumor promoter and a therapeutic target for PC.