ASAP3 upregulation contributes to colorectal carcinogenesis and indicates poor survival outcome

Summary

The function and clinical implication of ArfGAP With SH3 Domain, Ankyrin Repeat And PH Domain 3 (ASAP3) in colorectal cancer (CRC) remains undefined. In the present study, we showed that the expression level of ASAP3 was dramatically increased in CRC and its upregulation was associated with American Joint Committee on Cancer (AJCC) stage (P<0.001) and poor prognosis (P=0.0022). The combination of AJCC stage and ASAP3 expression improved the prediction of survival in CRC patients. Suppression of ASAP3 inhibited cell proliferation by inducing G1-phase arrest without influencing apoptosis. ASAP3 promoted growth of colon tumors in mice with colitis. ASAP3 accelerated cell invasion and migration in vitro. Increased ASAP3 was associated with activation of the NF-κB canonical pathway in CRC. Upregulation of ASAP3 increased the phosphorylation and nuclear translocation of p65 NF-κB subunit. Mechanistically, ASAP3 interact with NEMO and could reduce the polyubiquitinylation of NEMO. Overall, ASAP3 might regulate NF-κB via binding to NEMO. ASAP3 acts as an oncogene in colonic cancer and could be a potential biomarker of colon carcinogenesis.

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