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01-02-2016 | Research Article

HIF-2α regulates CDCP1 to promote PKCδ-mediated migration in hepatocellular carcinoma

Authors: Manqing Cao, Junrong Gao, Hongyuan Zhou, Jiafei Huang, Abin You, Zhigui Guo, Feng Fang, Wei Zhang, Tianqiang Song, Ti Zhang

Published in: Tumor Biology | Issue 2/2016

Abstract

Overexpression of CUB domain-containing protein 1 (CDCP1), a transmembrane glycoprotein and major substrate of Src family kinases (SFKs), always indicates unfavorable outcomes in various cancers. The characteristics of CDCP1 in hepatocellular carcinoma (HCC) have not been assessed. Most recently, CDCP1 was identified as a specific target gene of HIF-2α in clear cell renal carcinoma (CC-RCC). However, considering the role of HIF-2α in the progression of HCC is highly controversial, it is necessary to figure out whether HIF-2α and CDCP1 play a significant part in the metastasis of HCC. Our results showed that HIF-2α and CDCP1 were both induced by hypoxia, and the activation of CDCP1 was HIF-2α dependent. CDCP1 was governed by HIF-2α at mRNA and protein levels in HCC cell lines. Moreover, knocking down of HIF-2α not only inhibited cell invasion but also impaired the expression of Tyr³¹¹ phosphorylation of protein kinase Cδ (PKCδ) which is a downstream factor of CDCP1 and has been reported to induce malignant migration in various tumors. Analysis of human HCC samples showed a negative correlation of CDCP1 expression with disease-free survival, and CDCP1 was an independent prognostic factors of disease-free survival. Taken together, these data demonstrated that HIF-2α could promote HCC cell migration by regulating CDCP1, and targeting HIF-2α-CDCP1-PKCδ pathway might be effective to inhibit HCC metastasis.

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Title: HIF-2α regulates CDCP1 to promote PKCδ-mediated migration in hepatocellular carcinoma
Authors: Manqing Cao
Junrong Gao
Hongyuan Zhou
Jiafei Huang
Abin You
Zhigui Guo
Feng Fang
Wei Zhang
Tianqiang Song
Ti Zhang
Publication date: 01-02-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3527-7

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