Abstract:
:A common genetic mutation found in clear cell renal cell carcinoma (CC-RCC) is the loss of the von Hippel-Lindau (VHL) gene, which results in stabilization of hypoxia-inducible factors (HIFs), and contributes to cancer progression and metastasis. CUB-domain-containing protein 1 (CDCP1) was shown to promote metastasis in scirrhous and lung adenocarcinomas as well as in prostate cancer. In this study, we established a molecular mechanism linking VHL loss to induction of the CDCP1 gene through the HIF-1/2 pathway in renal cancer. Also, we report that Fyn, which forms a complex with CDCP1 and mediates its signaling to PKCδ, is a HIF-1 target gene. Mechanistically, we found that CDCP1 specifically regulates phosphorylation of PKCδ, but not of focal adhesion kinase or Crk-associated substrate. Signal transduction from CDCP1 to PKCδ leads to its activation, increasing migration of CC-RCC. Furthermore, patient survival can be stratified by CDCP1 expression at the cell surface of the tumor. Taken together, our data indicates that CDCP1 protein might serve as a therapeutic target for CC-RCC.
journal_name
Proc Natl Acad Sci U S Aauthors
Razorenova OV,Finger EC,Colavitti R,Chernikova SB,Boiko AD,Chan CK,Krieg A,Bedogni B,LaGory E,Weissman IL,Broome-Powell M,Giaccia AJdoi
10.1073/pnas.1011777108subject
Has Abstractpub_date
2011-02-01 00:00:00pages
1931-6issue
5eissn
0027-8424issn
1091-6490pii
1011777108journal_volume
108pub_type
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