Keratin 6A is expressed at the invasive front and enhances the progression of colorectal cancer.

Keratins are intermediate filament proteins in epithelial cells, and they are important for cytoskeletal organization. Keratin 6A (KRT6A), classified as a type II keratin, is normally expressed in stratified squamous epithelium and squamous cell carcinomas. Little is known about the expression and role of KRT6A in adenocarcinomas. We investigated the clinicopathological and molecular biological significance of KRT6A in colorectal adenocarcinoma. Immunostaining of our institution's colorectal adenocarcinoma cases demonstrated that KRT6A showed significantly stronger expression at the invasive front than the tumor center (p < 0.0001). The high-KRT6A-expression cases (n = 47) tended to have a high budding grade associated with significantly worse prognoses. A multivariate analysis revealed that the KRT6A expression status was an independent prognostic factor for overall survival (p = 0.0004), disease-specific survival (p = 0.0097) and progression-free survival (p = 0.0033). The correlation between KRT6A and patient prognoses was also validated in an external cohort from a published dataset. To determine the function of KRT6A in vitro, KRT6A was over-expressed in three colon cancer cell lines, DLD-1, SW620, and HCT 116. KRT6A overexpression increased migration and invasion in DLD-1, but did not in SW620 and HCT116. In three-dimensional sphere-forming culture, KRT6A expression enhanced the irregular protrusion around the spheroid in DLD-1. Our findings in the present study indicated that KRT6A expression is a valuable prognostic marker of colorectal cancer and KRT6A may be involved the molecular mechanism in the progression of invasive areas of colorectal cancer.