title: Tyrosine phosphatase SHP2 increases cell motility in triple-negative breast cancer through the activation of SRC-family kinases.
abstract: 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.
authors.affiliation: Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Sausgruber
authors.affiliation: Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland.
authors.forename: M-M
authors.initials: MM
authors.lastname: Coissieux
authors.affiliation: Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Britschgi
authors.affiliation: 1] Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland [2] Koch Institute for Integrated Cancer Research, Massachusetts Institute for Technology, Cambridge, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wyckoff
authors.affiliation: 1] Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland [2] Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Aceto
authors.affiliation: 1] Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland [2] Analytical sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Leroy
authors.affiliation: 1] Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland [2] Swiss Institute of Bioinformatics, Basel, Switzerland.
authors.forename: M B
authors.initials: MB
authors.lastname: Stadler
authors.affiliation: Analytical sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Voshol
authors.affiliation: Analytical sciences and Imaging, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Bonenfant
authors.affiliation: Mechanisms of cancer, Friedrich Miescher Institute (FMI) for Biomedical Research, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Bentires-Alj
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D019061:src-Family Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11