Suppression of SHIP2 contributes to tumorigenesis and proliferation of gastric cancer cells via activation of Akt

Autor: Jie Da, Miao Miao Xiao, Yan Ye, Qun Li, Li Mei Guo, Lin Jie Zhang, Wang Lai Hu, Xudong Zhang, Jiegou Xu, Ji Qing Hao, Yan Mei Ge
Rok vydání: 2015
Předmět:
0301 basic medicine
medicine.medical_specialty
Cell Survival
Down-Regulation
Mice
Nude
medicine.disease_cause
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Downregulation and upregulation
Stomach Neoplasms
Internal medicine
Gastric mucosa
Tumor Cells
Cultured
Medicine
Animals
Humans
Inositol
Neoplasm Invasiveness
Protein kinase B
Cell Proliferation
business.industry
Gastroenterology
Phosphoric Monoester Hydrolases
Gene Expression Regulation
Neoplastic
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Cell Transformation
Neoplastic
chemistry
Gastric Mucosa
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Phosphatidylinositol-3
4
5-Trisphosphate 5-Phosphatases
Cancer cell
Cancer research
Heterografts
Signal transduction
business
Carcinogenesis
Proto-Oncogene Proteins c-akt
Neoplasm Transplantation
Proto-oncogene tyrosine-protein kinase Src
Signal Transduction
Zdroj: Journal of gastroenterology. 51(3)
ISSN: 1435-5922
Popis: The Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is implicated in diabetes, arthrosclerosis, and cancer. However, the role of SHIP2 in human gastric cancer remains unclear.The expression levels of SHIP2 in gastric cancer tissues, a panel of gastric cancer cell lines, and normal gastric epithelial cells were analyzed by immunohistochemistry (IHC), Western blot, and real-time quantitative RT-PCR (qRT-PCR). Gastric cancer cells with either overexpressed SHIP2 or co-overexpressed SHIP2 and Akt were analyzed to determine cell proliferation, colony formation, apoptosis, cell migration, and invasion assays. Normal gastric epithelial cells with knockdown SHIP2 or co-knockdown SHIP2 and Akt were subjected by anchorage-independent growth assays. The effect of SHIP2 on tumor growth in vivo was detected by xenograft tumorigenesis assays.SHIP2 was commonly downregulated in gastric cancer compared with normal gastric mucosa, and overexpression of SHIP2 inhibited cell proliferation, induced apoptosis, suppressed cell motility and invasion in gastric cancer cells in vitro, and retarded the growth of xenograft gastric tumors in vivo, while knockdown of SHIP2 in normal gastric epithelial cells promoted anchorage-independent growth. Moreover, overexpression of SHIP2 inactivated Akt, and upregulated p21, p27, and the pro-apoptotic protein Bim. Restoring Akt activation in gastric cancer cells largely blocked the inhibition of PI3K/Akt signaling by SHIP2 and reversed the inhibitory effect of SHIP2 on tumorigenesis and proliferation.This study demonstrates, for the first time, that SHIP2 is frequently downregulated in gastric cancer, and reduced SHIP2 expression promotes tumorigenesis and proliferation of gastric cancer via activation of the PI3K/Akt signaling.
Databáze: OpenAIRE
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