Anoctamin 5 promotes colon cancer progression and predicts poor prognosis.

Anoctamin 5 (ANO5), a member of the anoctamin/transmembrane protein 16 family, has been implicated in various cancers; however, its role in colon cancer (CC) remains unclear. We examined ANO5 expression in CC cell lines and human tumor tissues and investigated its functional significance. ANO5 knockdown using small interfering RNA markedly suppressed proliferation, migration, and invasion of HCT116 and LoVo cells, while inducing G0/G1 cell-cycle arrest and apoptosis. Microarray and validation analyses revealed activation of the TP53-BAX-CASP3 apoptotic pathway and regulation of CDKN1A and CDK2, suggesting that ANO5 modulates both apoptosis and G1/S checkpoint progression. Immunohistochemistry of tumors from 200 patients with stage II/III CC demonstrated high ANO5 expression in 52% of cases. High expression was significantly associated with poorer outcomes, with 5-year relapse-free survival (62.6% vs. 87.3%, p < 0.001) and overall survival (74.0% vs. 94.8%, p < 0.001) markedly worse in the high-expression group. Multivariate analyses confirmed high ANO5 expression as an independent prognostic factor. Collectively, ANO5 promotes tumor cell growth, survival, and motility, and its high expression predicts unfavorable clinical outcomes, indicating its potential as a prognostic biomarker and therapeutic target in CC.