Overexpressed ACP5 has prognostic value in colorectal cancer and promotes cell proliferation and tumorigenesis via FAK/PI3K/AKT signaling pathway.

ABSTRACT

The tartrate-resistant acid phosphatase (TRAP/ACP5) correlated with tumor progression in many malignancies. However, the role of ACP5 in colorectal cancer (CRC) has not been thoroughly elucidated. In this study, we sought to identify the role for ACP5 in CRC progression. Immunohistochemistry revealed that high ACP5 expression is positively associated with tumor size, tumor classification, lymph node metastasis, distant metastasis and advanced stage cancer in 285 CRC patients. Moreover, high ACP5 expression was significantly associated with poor overall survival and disease-free survival. Then, ectopic expression of ACP5 promoted tumor cell proliferation and invasion, whereas suppression of ACP5 expression resulted in decreased cell proliferation and invasion in colorectal cell lines in vitro. And, inhibition of ACP5 also inhibited growth of engrafted tumors in vivo. Furthermore, we found that ACP5 overexpression positively regulated p-FAK, p-PI3K and p-AKT in CRC cells. ACP5 depletion showed the opposite effects. What's more, overexpression of FAK in CRC cells could restore the reduced abilities of cell proliferation and invasion caused by siRNAs-ACP5. Finally, we found the inhibition of activity by Akt inhibitors, MK2206, could partially decrease the positive effects of ACP5 on CRC cell proliferation and invasion. In conclusion, our results suggest that overexpressed ACP5 might serve as an indicator for poor prognosis in colorectal cancer patients through regulation of FAK/PI3K/AKT signaling pathway, which might be a potential therapeutic approach for colorectal cancer therapy.