CD44v6 Promotes Proliferation, Migration, and Invasion in Cholangiocarcinoma Cells, but Lacks Independent Prognostic Significance

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile duct epithelium. Alt-hough the CD44v6 splice variant is implicated in the progression of numerous cancers, its functional role and clinical relevance in CCA remain poorly defined. This study investi-gated the biological functions and prognostic significance of CD44v6 in CCA. We silenced CD44v6 expression in human CCA cell lines (HuCCA-1 and KKU-M213), and assessed its impact on proliferation, migration, invasion, and epithelial-mesenchymal-transition markers. Additionally, CD44v6 expression was evaluated by immunohistochemistry in 61 patient tumors and correlated with clinicopathological data. Silencing of CD44v6 in vitro modestly reduced cell proliferation by approximately 25% but profoundly impaired migration and invasion by over 50% and was associated with a mesenchy-mal-to-epithelial transition, evidenced by a decrease in the mesenchymal marker Vi-mentin and an increase of epithelial marker, Claudin-1. In patient tissues, however, CD44v6 expression showed no significant correlation with clinicopathological parame-ters or overall survival. Our findings established CD44v6 as a significant mediator of ma-lignant cell behaviors in CCA, particularly migration and invasion. Lack of association between CD44v6 expression and clinicopathological parameters suggests CD44v6’s role is highly context-dependent, positioning it not as a standalone prognostic marker, but as a potential therapeutic target against metastatic progression of CCA.