ITEM METADATA RECORD
Title: The tyrosine phosphatase PTPRO sensitizes colon cancer cells to anti-EGFR therapy through activation of SRC-mediated EGFR signaling
Authors: Abbasi Asbagh, Layka
Vazquez, Iria
Vecchione, Loredana
Budinska, Eva
De Vriendt, Veerle
Baietti, Maria Francesca
Steklov, Mikhail
Jacobs, Bart
Hoe, Nicholas
Singh, Sharat
Imjeti, Naga-Sailaja
Zimmermann, Pascale
Sablina, Anna # ×
Tejpar, Sabine #
Issue Date: Oct-2014
Series Title: Oncotarget vol:5 issue:20 pages:10070-10083
Abstract: Inappropriate activation of epidermal growth factor receptor (EGFR) plays a causal role in many cancers including colon cancer. The activation of EGFR by phosphorylation is balanced by receptor kinase and protein tyrosine phosphatase activities. However, the mechanisms of negative EGFR regulation by tyrosine phosphatases remain largely unexplored. Our previous results indicate that protein tyrosine phosphatase receptor type O (PTPRO) is down-regulated in a subset of colorectal cancer (CRC) patients with a poor prognosis. Here we identified PTPRO as a phosphatase that negatively regulates SRC by directly dephosphorylating Y416 phosphorylation site. SRC activation triggered by PTPRO down-regulation induces phosphorylation of both EGFR at Y845 and the c-CBL ubiquitin ligase at Y731. Increased EGFR phosphorylation at Y845 promotes its receptor activity, whereas enhanced phosphorylation of c-CBL triggers its degradation promoting EGFR stability. Importantly, hyperactivation of SRC/EGFR signaling triggered by loss of PTPRO leads to high resistance of colon cancer to EGFR inhibitors. Our results not only highlight the PTPRO contribution in negative regulation of SRC/EGFR signaling but also suggest that tumors with low PTPRO expression may be therapeutically targetable by anti-SRC therapies.
URI: 
ISSN: 1949-2553
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Molecular Digestive Oncology (+)
LUCA School of Arts
Laboratory for Mechanisms of Cell Transformation
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science