CDK14 involvement in proliferation migration and invasion of esophageal cancer

Lingling Chen; Yayun Wang; Wenyan Jiang; Runzhou Ni; Yuchan Wang; Sujie Ni

doi:10.21037/atm.2019.11.105

CDK14 involvement in proliferation migration and invasion of esophageal cancer

Ann Transl Med. 2019 Nov;7(22):681. doi: 10.21037/atm.2019.11.105.

Authors

Lingling Chen¹, Yayun Wang², Wenyan Jiang³, Runzhou Ni⁴, Yuchan Wang⁵, Sujie Ni⁶

Affiliations

¹ Department of Gastroenterology, Huashan Hospital North, Fudan University, Shanghai 201907, China.
² Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
³ Department of Respiratory, Nantong First People Hospital, Nantong 226001, China.
⁴ Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China.
⁵ Department of Pathogenic Biology, Medical College, Nantong University, Nantong 226001, China.
⁶ Department of Medical Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China.

Abstract

Background: CDK14 has significant involvement in tumorigenesis of cancers including hepatocellular carcinoma, gastric carcinoma and breast cancer. In esophageal cancer, CDK14 is useful as a prognostic marker and as a predictor of response to chemotherapy. However, the exact mechanism of CDK14 n chemotherapy for esophageal squamous cell carcinoma (ESCC) has not been explored.

Methods: Western blots and immunohistochemistry (IHC) analysis were performed to analyse the expression of CDK14 in ESCC. Co-immunoprecipitation and immunofluorescence assays were used to explore the mechanism of CDK14 involvement in ESCC. Colony formation assays and proliferation assays were used to investigate the function of CDK14 in ESCC. At last, we constructed two truncated mutants of CDK14 by the PCR technology to research the functional structural domain.

Results: Western blots and IHC analysis showed that CDK14 expression was higher n tumor tissues and cell lines than that in normal tissues. IHC staining revealed that CDK14 positively correlated with clinical pathological variables of tumor size (P=0.001), tumor grade (P=0.004), Ki-67 (P=0.012) and survival (P=0.000). Immunoprecipitation and immunofluorescence assays revealed that CDK-activating kinase (CAK), namely CDK7/CCNH complex physically interacted and was collocated with CDK14 in the cell nucleus. This direct interaction increased CDK14 phosphorylation and inhibited Rb function through phosphorylation. In vitro starvation and refeeding assays demonstrated that CDK14 expression was related to proliferation of ESCC cells. Overexpression of CDK14 in Eca109 cells increased colony formation and reduced sensitivity to cisplatin. Overexpressing CDK7 with CDK14 strengthened these effects, demonstrating that CDK7 was a major component in CDK14 activation.

Conclusions: Expression of CDK14 worsened the effects of cisplatin chemotherapy by promoting ESCC proliferation.

Keywords: CDK14; CDK7/CCNH complex; Esophageal squamous cell carcinoma (ESCC); proliferation.