PAR4 overexpression promotes colorectal cancer cell proliferation and migration.

Protease-activated receptor 4 (PAR4), a member of the G-protein-coupled receptor family, was previously identified to be involved in the progression of cancer. Previous study revealed that the expression of PAR4 was increased in colorectal cancer tissues compared with the associated normal tissues, particularly in positive lymph node and poorly differentiated types of cancer. We hypothesized that PAR4 serves a function in the progression of colorectal cancer. In the present study, overexpression of PAR4 in colorectal cancer LoVo cells promoted proliferation, anchorage-independent growth and migration. In vivo , PAR4 increased LoVo cell tumorgenicity. In contrast, knockdown of PAR4 in HT-29 cells decreased proliferation, anchorage-independent growth and migration. Mechanistic studies revealed that PAR4 increased the phosphorylation of extracellular-signal-regulated kinase 1/2 in colorectal cancer cells, which is the potential molecular mechanism that promotes cellular proliferation and migration. Taken together, the results of the present study indicated that overexpression of PAR4 promoted colorectal cancer cell proliferation, survival and metastasis, indicating that PAR4 is a promising therapeutic target for preventing colon cancer progression.