Carboxypeptidase A4 promotes cell growth via activating STAT3 and ERK signaling pathways and predicts a poor prognosis in colorectal cancer.

Carboxypeptidase A4 (CPA4) is a novel cancer-related gene that is aberrantly expressed in various malignant tumors. However, the roles and mechanisms of CPA4 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions and mechanisms by which CPA4 promotes CRC progression. Quantitative real-time PCR (qRT-PCR) and western blot showed that CPA4 mRNA and CPA4 protein levels were up-regulated in CRC compared to levels in adjacent normal tissue. Immunohistochemistry (IHC) results indicating high CPA4 levels were positively associated with poor prognoses. In addition, Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays demonstrated that CPA4 overexpression facilitated the growth of CRC cells, whereas CPA4 knockdown resulted in decreased proliferation, G1/S phase transition arrest, and apoptosis. Subcutaneous tumorigenesis was performed in nude mice to confirm the tumor-promoting effects of CPA4 in vivo. Western blot revealed that activation of the STAT3 and ERK pathways is one of the oncogenic functions of CPA4 in CRC. Accordingly, CPA4 promotes CRC cell growth via activating the STAT3 and ERK pathways and may be a prognostic factor or therapeutic target for CRC.