CEACAM6 silencing suppresses tumour growth and sensitises cholangiocarcinoma to cisplatin

Abstract Background The CEACAM family, a major subgroup of the carcinoembryonic antigen (CEA) family, is widely expressed in normal and neoplastic tissues. Although CEACAM6 overexpression has been reported in cholangiocarcinoma (CCA), the molecular mechanisms by which it modulates chemosensitivity in CCA remain unclear. Methods We began by analysing CEACAM6 expression in CCA using the TCGA database, then confirmed its clinical relevance in our institutional patient cohorts. Through cellular assays, animal models, and RNA sequencing, we found that silencing CEACAM6 inhibits tumour growth and identified its key underlying mechanisms. Results Our data showed that CEACAM6 expression is significantly elevated in CCA and serves as an independent prognostic marker. Functional validation by CEACAM6 silencing demonstrated that loss of CEACAM6 markedly suppressed tumour cell proliferation and clonogenicity in vitro, potentiated cisplatin‐induced DNA damage and apoptosis, and inhibited tumour growth in vivo. Conclusions CEACAM6 silencing was shown to suppress ribosome biogenesis and augment DNA damage, thereby inhibiting tumour growth and sensitising CCA to cisplatin. Our research highlights CEACAM6 as a potential therapeutic target that could help improve the therapeutic efficacy of cisplatin in CCA.