TMPRSS4 Promotes Cell Proliferation and Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma by Activating ERK1/2 Signaling Pathway

• Published in: Frontiers in oncology 2021-03, Vol.11, p.628353-628353
• Main Authors: Gu, Jianyou, Huang, Wenjie, Zhang, Junfeng, Wang, Xianxing, Tao, Tian, Yang, Ludi, Zheng, Yao, Liu, Songsong, Yang, Jiali, Zhu, Liwei, Wang, Huaizhi, Fan, Yingfang
• Format: Article
• Language: English
• Subjects: apoptosis; ERK1/2; Oncology; pancreatic ductal adenocarcinoma; proliferation; TMPRSS4
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2021.628353

Transmembrane protease serine 4 (TMPRSS4) is upregulated in various kinds of human cancers, including pancreatic cancer. However, its biological function in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the current study, real-time qPCR, immunohistochemical staining, Western blotting, and database (Cancer Genome Atlas and Gene Expression) analysis revealed remarkable overexpression of TMPRSS4 in PDAC tissue as compared to non-tumor tissue. The TMPRSS4 overexpression was associated with poor prognosis of PDAC patients. Moreover, multivariate analysis revealed that TMPRSS4 serves as an independent risk factor in PDAC. We performed gain-and loss-of-function analysis and found that TMPRSS4 promotes cellular proliferation and inhibits apoptosis of PDAC cells both and . Furthermore, we showed that TMPRSS4 might promote cell proliferation and inhibit apoptosis through activating ERK1/2 signaling pathway in pancreatic cancer cells. These findings were validated by using ERK1/2 phosphorylation inhibitor SCH772984 both and . Taken together, this study suggests that TMPRSS4 is a proto-oncogene, which promotes initiation and progression of PDAC by controlling cell proliferation and apoptosis. Our findings indicate that TMPRSS4 could be a promising prognostic biomarker and a therapeutic target for the treatment of pancreatic cancer.