Upregulation of ASAP3 contributes to colorectal carcinogenesis and indicates poor survival outcome. Issue 8 (14th June 2017)

• Record Type: Journal Article
• Authors: Tian, Haiying; Qian, Jin; Ai, Luoyan; Li, Yueyuan; Su, Wenyu; Kong, Xian‐Ming; Xu, Jie; Fang, Jing‐Yuan
• Is Part Of: Cancer science. Volume 108:Issue 8(2017)
• Page Start: 1544
• Page End: 1555
• Publication Date: 2017-06-14
• Subjects: ASAP3 -- colorectal cancer -- NEMO -- NFκB -- oncogene; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13281
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : 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 stage ( P < 0.001) and poor prognosis ( P = 0.0022). The combination of 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, and accelerated cell invasion and migration in vitro . Increased ASAP3 was associated with activation of the nuclear factor‐κB (NF‐κB) canonical pathway in CRC. Upregulation of ASAP3 increased the phosphorylation and nuclear translocation of the p65 NF‐κB subunit. Mechanistically, ASAP3 interacts with NF‐κB essential modulator (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. Abstract : Upregulation of ASAP3 is associated with poor prognosis in colorectal cancer. ASAP3 might act as an oncogene in colorectal cancer through NF‐κB pathway.