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

被引：58

作者：

Sausgruber, N. ^{[1
]}

Coissieux, M-M ^{[1
]}

Britschgi, A. ^{[1
]}

Wyckoff, J. ^{[1
,2
]}

Aceto, N. ^{[1
,3
]}

Leroy, C. ^{[1
,4
]}

Stadler, M. B. ^{[1
,5
]}

Voshol, H. ^{[4
]}

Bonenfant, D. ^{[4
]}

Bentires-Alj, M. ^{[1
]}

机构：

[1] Friedrich Miescher Inst FMI Biomed Res, Mechanisms Canc, CH-4058 Basel, Switzerland

[2] MIT, Koch Inst Integrated Canc Res, Cambridge, MA 02139 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA

[4] Novartis Inst Biomed Res, Analyt Sci & Imaging, Basel, Switzerland

[5] Swiss Inst Bioinformat, Basel, Switzerland

来源：

ONCOGENE | 2015年 / 34卷 / 17期

基金：

欧洲研究理事会;

关键词：

FOCAL ADHESION KINASE; GROWTH-FACTOR; IN-VIVO; C-SRC; MIGRATION; PAXILLIN; PHOSPHORYLATION; METASTASIS; TUMORS; DEPHOSPHORYLATION;

D O I：

10.1038/onc.2014.170

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2272 / 2278

页数：7

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