CDK11p110 plays a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells and is a potential drug target

Abstract

ABSTRACT Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with limited options for targeted therapy. The exploration of novel targeted therapies for combating ESCC is urgently needed. Cyclin-dependent kinases (CDKs) play important roles in the progression of cancers; however, the function of CDK11p110 (cyclin-dependent kinase 11p110) in ESCC is still unknown. Here, we investigated the effects and molecular mechanisms of CDK11p110 in the proliferation and growth of ESCC by examining the expression of CDK11p110 in ESCC tissues and by detecting phenotypic changes in ESCC cells after CDK11p110 knockdown or overexpression in vitro and in vivo. According to the tissue microarray analysis, compared with its expression level in normal tissues, the expression level of CDK11p110 was significantly elevated in ESCC tissues; this result was in concordance with the data in TCGA (The Cancer Genome Atlas) datasets. In addition, RNAi-mediated CDK11p110 silencing exerted a substantial inhibitory effect on the proliferation, clonogenicity and migration ability of ESCC cells. Further study indicated that CDK11p110 knockdown arrested ESCC cells in the G2/M phase of the cell cycle and induced cell apoptosis. Moreover, stable shRNA-mediated CDK11p110 knockdown inhibited tumor growth in an ESCC xenograft model, and overexpression of CDK11p110 enhanced tumor growth. In addition, the Ki67 proliferation index was closely associated with the elevation or depletion of CDK11p110 in vivo. In summary, this study provides evidence that CDK11p110 play a critical role in the tumorigenicity of ESCC cells, which suggests that CDK11p110 may be a promising therapeutic target in ESCC. Abbreviations: CDKs: cyclin-dependent kinases; CDK11: Cyclin-dependent kinase 11; CDK11p110: Cyclin-dependent kinase 11p110, the larger isomer of cyclin-dependent kinase 11; ESCC: esophageal squamous cell carcinoma; FACS: fluorescence-activated cell sorting; FDA: the Food and Drug Administration; TCGA: The Cancer Genome Atlas; TMA: tissue microarray.