title: A tyrosine phosphatase SHP2 gain-of-function mutation enhances malignancy of breast carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.|Department of Ultrasound, Zhongda Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Zhongqian
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.|Department of Clinical Medicine, Anhui Medical University, Hefei 230032, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Haoshu
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Danlei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Daoyan
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.|Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta 30322, GA, USA.
authors.forename: Chengkui
authors.initials: C
authors.lastname: Qu
authors.affiliation: Department of Pathophysiology, Anhui Medical University, Hefei 230032, China.
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D014443:Tyrosine; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: D61G mutation; SHP2; breast cancer; gain-of-function; tumor