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| 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
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| 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
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| Overall design |
ShcA mutant (R175Q) vs NT/ShcA cells
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| Contributor(s) |
Ursini-Siegel J, Cory S |
| Citation(s) |
23695548 |
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| Submission date |
Oct 19, 2012 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Sean Cory |
| E-mail(s) |
[email protected]
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| Organization name |
McGill
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| Department |
Goodman Cancer centre
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| Lab |
Hallett
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| Street address |
3649 Promenade Sir William Osler
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| City |
Montreal |
| State/province |
QC |
| ZIP/Postal code |
H3G 0B1 |
| Country |
Canada |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA178013 |
| 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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