title: HIF-2α regulates CDCP1 to promote PKCδ-mediated migration in hepatocellular carcinoma.
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 Tyr(311) 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.
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Manqing
authors: M
authors: Cao
authors: Academy of Medical Image, Tianjin Medical University, Tianjin, People's Republic of China.
authors: Junrong
authors: J
authors: Gao
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Hongyuan
authors: H
authors: Zhou
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Jiafei
authors: J
authors: Huang
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Abin
authors: A
authors: You
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Zhigui
authors: Z
authors: Guo
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Feng
authors: F
authors: Fang
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China. tjchi@hotmail.com.
authors: Tianqiang
authors: T
authors: Song
authors: Department of Hepatobiliary Surgery, National Clinical Research Center for Cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, 24 Bin Shui Road, Hexi District, Tianjin, 300060, People's Republic of China. zhangti@tjmuch.com.
authors: Ti
authors: T
authors: Zhang
mesh_terms: D000111:Acetylcysteine; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000111:Acetylcysteine; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D051745:Protein Kinase C-delta; D000099162:Endothelial PAS Domain-Containing Protein 1; C432044:CDCP1 protein, human
keywords: CDCP1; HIF-2α; Hepatocellular carcinoma; Metastasis; PKCδ