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Series GSE41718 Query DataSets for GSE41718
Status Public on Aug 07, 2013
Title The ShcA PTB Domain Functions as a Biological Sensor of Phospho-tyrosine Signaling During Breast Cancer Progression
Organism Mus musculus
Experiment type Expression profiling by array
Summary The ShcA adaptor possesses two phosphotyrosine binding motifs, which include an SH2 and a PTB domain. In the majority of cases, ShcA utilizes its PTB domain to engage activated receptor tyrosine kinases (RTKs). To establish the mportance of this domain during mammary tumorigenesis, we employed a ShcA mutant (R175Q) that no longer binds phospho-tyrosine residues via its PTB domain. We demonstrate that the ShcR175Q mutant delays mammary tumor onset n MMTV/MT transgenic animals. Paradoxically, we observe a robust increase in the growth and angiogenesis of emerging mammary tumors. ShcR175Q-expressing breast cancer cells increase fibronectin secretion and possess elevated levels f integrin α5/β1, the principle fibronectin receptor. Sustained integrin engagement activates Src, which in turn phosphorylates pro-angiogenic RTKs, including PDGFR, FGFR and Met, leading to increased VEGF secretion from ShcR175Q-xpressing breast cancer cells. Finally, we describe a ShcR175Q-dependent gene signature that stratifies breast cancer patients with a high microvessel density. This is the first study to demonstrate that intracellular signaling pathways ownstream of the ShcA PTB domain both positively and negatively regulate tumorigenesis during the various stages of breast cancer progression
Overall design ShcA mutant (R175Q) vs NT/ShcA cells
Contributor(s) Ursini-Siegel J, Cory S
Citation(s) 23695548
Submission date Oct 19, 2012
Last update date Nov 01, 2017
Contact name Sean Cory
Organization name McGill
Department Goodman Cancer centre
Lab Hallett
Street address 3649 Promenade Sir William Osler
City Montreal
State/province QC
ZIP/Postal code H3G 0B1
Country Canada
Platforms (1)
GPL11202 Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
Samples (8)
GSM1023100 R175Q 1
GSM1023101 R175Q 2
GSM1023102 nT 1
BioProject PRJNA178013

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE41718_RAW.tar 122.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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