CDK14 involvement in proliferation migration and invasion of esophageal cancer

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.

CircCDK14 Promotes Tumor Progression and Resists Ferroptosis in Glioma by Regulating PDGFRA

“…As the host gene of circCDK14, CDK14 acts as a cyclin-dependent kinase that regulates cell cycle progression and cell proliferation. CDK14 involves in tumorigenesis of various cancers including glioma [30,32,33]. Studies shows that the interaction between CDK14 and cyclin Y can promote noncanonical Wnt signaling in human hepatocellular carcinoma [34].…”

Notch1mutation drives clonal expansion in normal esophageal epithelium but impairs tumor growth

“…Our transcriptional analysis suggests some potential mechanisms. Examples include transcripts of genes that promote growth and invasiveness in ESCC cells, such as Nrp2, Cdk14 and Sox9 which are more highly expressed in Notch1 wild type than null esophageal cells [35][36][37] . Conversely, transcription of Cldn7 which represses ESCC invasiveness is upregulated in Notch1 -/cells 38,39 .…”

The Candidate IBD Risk Gene CCNY Is Dispensable for Intestinal Epithelial Homeostasis

“…Earlier studies suggested that CDK14 is the main regulator of cyclin-Y-dependent Wnt signaling [ 11 , 34 ], and we observed exceedingly low levels of CDK14 specifically in the intestinal epithelium [ 22 , 23 ]. CDK14 has been shown to interact with other cyclins as well, such as cyclin B to activate the Wnt pathway in breast cancer [ 35 ], cyclin D3 to regulate cell cycle progression and proliferation in mammalian cells [ 36 ], and the CDK7/cyclin H complex to regulate proliferation and migration in esophageal cancer [ 37 ]. It should be noted that previous studies suggested functional redundancy among the human PFTAIRE/PCTAIRE family kinases (CDK 14–18) [ 11 , 38 ].…”