CDK8 regulates the angiogenesis of pancreatic cancer cells in part via the CDK8-β-catenin-KLF2 signal axis.

Abstract:

BACKGROUND:CDK8 is associated with the transcriptional Mediator complex and has been shown to regulate several transcription factors implicated in cancer. As a pancreatic cancer oncogene, the role of CDK8 in cancer angiogenesis remains unclear. Here, we investigated the contribution of CDK8 in pancreatic cancer angiogenesis and examined the underlying molecular mechanisms. METHODS:CDK8 expression was evaluated via immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of pancreatic cancer patients. The effects of silencing or overexpressing CDK8 on cancer angiogenesis were assessed in vitro by western blotting assays in pancreatic cancer cell lines and in vivo with nude mice xenograft models. RESULTS:Compared with adjacent normal tissues, pancreatic cancer tissues showed upregulation of CDK8 expression, which was inversely correlated with T grade, liver metastasis, size, lymph node metastasis and poor survival. CDK8 overexpression promoted angiogenesis in pancreatic cancer via activation of the CDK8-β-catenin-KLF2 signaling axis, as demonstrated by the upregulation and downregulation of signals representing the rate-limiting steps in angiogenesis. Silencing CDK8 inhibited angiogenesis in pancreatic cancer in vitro. Additionally, these results were confirmed in nude mice xenograft models in vivo. CONCLUSIONS:CDK8 promotes angiogenesis in pancreatic cancer via activation of the CDK8-β-catenin-KLF2 signaling axis, thus providing valid targets for the treatment of pancreatic cancer.

journal_name

Exp Cell Res

authors

Wei R,Kong L,Xiao Y,Yuan H,Song Y,Wang J,Yu H,Mao S,Xu W

doi

10.1016/j.yexcr.2018.05.033

subject

Has Abstract

pub_date

2018-08-15 00:00:00

pages

304-315

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(18)30304-5

journal_volume

369

pub_type

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