The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Dong, Ying, He, Yaowu, de Boer, Leonore, Stack, M. Sharon, Lumley, John W., Clements, Judith A. and Hooper, John D. (2012) The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration. Journal of Biological Chemistry, 287 13: 9792-9803. doi:10.1074/jbc.M111.335448

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Author Dong, Ying
He, Yaowu
de Boer, Leonore
Stack, M. Sharon
Lumley, John W.
Clements, Judith A.
Hooper, John D.
Title The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2012-03-23
Year available 2012
Sub-type Article (original research)
DOI 10.1074/jbc.M111.335448
Open Access Status File (Publisher version)
Volume 287
Issue 13
Start page 9792
End page 9803
Total pages 12
Place of publication Bethesda, MD United States
Publisher American Society for Biochemistry and Molecular Biolog
Language eng
Abstract Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/ EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/ RAF/MEK/ERK pathway.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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Created: Mon, 20 Jul 2015, 13:46:53 EST by Joanne PRESTON on behalf of Mater Research Institute-UQ