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A tyrosine phosphatase SHP2 gain-of-function mutation enhances malignancy of breast carcinoma.

ABSTRACT: Evidence suggests that Src homologous protein phosphotyrosyl phosphatase 2 (SHP2) mutations promote cancer development in several solid tumours. In this study, we focused on the in vivo and in vitro effects of an SHP2 mutation on the breast cancer phenotype to determine whether this mutation is correlated with a malignant phenotype.Mutant PTPN11 cDNA (D61G) was transduced into MDA-MB231 and MCF-7 cells. The effects of the D61G mutation on tumourigenesis and malignant behaviours, such as cell adhesion, proliferation, migration and invasion, were examined. Potential underlying molecular mechanisms, i.e., activation of the Gab1-Ras-Erk axis, were also examined.In vitro experiments revealed that tumour adhesion, proliferation, migration and invasion were significantly increased in the SHP2 D61G mutant groups. Consistently, in vivo experiments also showed that the tumour sizes and weights were increased significantly in the SHP2 D61G-MB231 group (p < 0.001) in association with tumour metastasis. Mechanistically, the PTPN11 mutation resulted in activation of the Ras-ErK pathway. The binding between Gab1 and mutant SHP2 was significantly increased.Mutant SHP2 significantly promotes tumour migration and invasion at least partially through activation of the Gab1-Ras-Erk axis. This finding could have direct implications for breast cancer therapy.


PROVIDER: S-EPMC4868712 | BioStudies | 2016-01-01T00:00:00Z

REPOSITORIES: biostudies

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