Tyrosine phosphatase SHP2 increases cell motility in triple-negative breast cancer through the activation of SRC-family kinases

Tumor cell migration has a fundamental role in early steps of metastasis, the fatal hallmark of cancer. In the present study, we investigated the effects of the tyrosine phosphatase, SRC-homology 2 domain-containing phosphatase 2 (SHP2), on cell migration in metastatic triple-negative breast cancer...

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Bibliographic Details
Published in:Oncogene 2015-04, Vol.34 (17), p.2272-2278
Main Authors: Sausgruber, N, Coissieux, M-M, Britschgi, A, Wyckoff, J, Aceto, N, Leroy, C, Stadler, M B, Voshol, H, Bonenfant, D, Bentires-Alj, M
Format: Article
Language:English
Subjects:
Animal models
Animals
Biochemical analysis
Breast cancer
Breast Neoplasms - enzymology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement
Chemotaxis
Development and progression
Female
Fluorescence resonance energy transfer
Genetic aspects
Health aspects
Heterografts
Homology
Humans
Metastases
Mice
Motility
Neoplasm Invasiveness
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Neoplasm Transplantation
Phosphatase
Phosphotransferases
Properties
Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 11 - metabolism
Protein-tyrosine-phosphatase
Rodents
Src protein
src-Family Kinases - genetics
src-Family Kinases - metabolism
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Summary:Tumor cell migration has a fundamental role in early steps of metastasis, the fatal hallmark of cancer. In the present study, we investigated the effects of the tyrosine phosphatase, SRC-homology 2 domain-containing phosphatase 2 (SHP2), on cell migration in metastatic triple-negative breast cancer (TNBC), an aggressive disease associated with a poor prognosis for which a targeted therapy is not yet available. Using mouse models and multiphoton intravital imaging, we have identified a crucial effect of SHP2 on TNBC cell motility in vivo. Further, analysis of TNBC cells revealed that SHP2 also influences cell migration, chemotaxis and invasion in vitro. Unbiased phosphoproteomics and biochemical analysis showed that SHP2 activates several SRC-family kinases and downstream targets, most of which are inducers of migration and invasion. In particular, direct interaction between SHP2 and c-SRC was revealed by a fluorescence resonance energy transfer assay. These results suggest that SHP2 is a crucial factor during early steps of TNBC migration to distant organs.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2014.170