Up-regulated CKS2 promotes tumor progression and predicts a poor prognosis in human colorectal cancer

摘要

Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a cyclin-dependent kinase-interacting protein, which is essential for cell cycle regulation. Elevated expression of CKS2 has been demonstrated in multiple types of human malignancies. However, the clinical significance, oncogenic functions and related mechanisms of CKS2 in colorectal cancer (CRC) remain largely unexplored. In this study, data from Oncomine database revealed that CKS2 is significantly up-regulated in CRC tissues compared with their normal counterparts. Immunohistochemical analysis of a CRC tissue microarray demonstrated that elevated CKS2 expression is closely associated with enhanced TNM stage, larger tumor size and a poor prognosis in patients with CRC. Multivariate Cox regression analysis revealed that CKS2 and TNM stage are two independent prognostic factors for CRC. Suppression of CKS2 expression resulted in decreased cell viability, increased cell apoptosis, cell cycle arrest and reduced expression of cyclins in Caco-2 and SW620 cells. Furthermore, gain and loss of function studies demonstrated that CKS2 promotes cell invasion in CRC cells through regulating claudin1. Taken together, our study reveal that CKS2 is promising prognostic indicator and contributes to tumor progression in CRC, and support that CKS2-related signaling may represent a novel target for CRC therapy.