Abstract
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 in vitro and in vivo. 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 in vitro and in vivo. 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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer (PC) and the fourth most lethal malignancy
We found that Transmembrane protease serine 4 (TMPRSS4) is significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines
The outcome of this study revealed the critical role of TMPRSS4 in mediating cell proliferation and apoptosis in pancreatic cancer cells via the ERK1/2 signaling pathway
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer (PC) and the fourth most lethal malignancy. It has a poor prognosis with the five-year survival rate of only 10% [1]. There has not been much progress in the early prognosis and treatment in pancreatic cancer as compared to other malignancies, such as breast and colorectal cancers [2]. Clinical management of pancreatic cancer poses several challenges such as prevention, early diagnosis at a curable stage, and effective biomarkers for its precise detection [3]. There is an unmet need for the development of sensitive, as well as specific therapeutic targets and an in-depth understanding of the regulatory mechanisms that mediate the development of pancreatic cancer.
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