title: Grb2-associated binder 2 silencing impairs growth and migration of H1975 cells via modulation of PI3K-Akt signaling.
abstract: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death and often has a poor prognosis. Investigation of NSCLC cancer cell migration, invasion and development of strategies to block this process is essential to improve the disease prognosis. In this study, we tested our hypothesis that Grb2-associated binder 2 (Gab2) regulate NSCLC cancer cell H1975 malignant biological behaviors, and silencing Gab2 reduced H1975 cellular colony forming ability, migration and invasion. Moreover, silenced cells present defects in phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (Akt) signaling, and reduced expression/activity of matrix metallopeptidase (MMP)-2/9. Furthermore, in Gab2 siRNA-transfected cells, we detected a decrease in signal transducer and activator of transcription 3 (STAT3) phosphorylation and nuclear translocation. In vivo, Gab2 siRNA cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and PI3K-Akt signaling inhibition. These results indicate that Gab2 is a key factor in H1975 tumor migration, invasion, suggesting that Gab2 can be a novel therapeutic target in NSCLC.
authors.affiliation: Department of Oncology, People's Hospital of Laiwu City No. 1 Xuehu Street, Changshao Road, Laiwu, Shandong, China.
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Wang
authors.affiliation: Department of Oncology, People's Hospital of Laiwu City No. 1 Xuehu Street, Changshao Road, Laiwu, Shandong, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Mou
authors.affiliation: Department of Hematology, People's Hospital of Laiwu City No. 1 Xuehu Street, Changshao Road, Laiwu, Shandong, China.
authors.forename: Xi Feng
authors.initials: XF
authors.lastname: Wu
authors.affiliation: Department of Oncology, People's Hospital of Laiwu City No. 1 Xuehu Street, Changshao Road, Laiwu, Shandong, China.
authors.forename: Jin Zhong
authors.initials: JZ
authors.lastname: Zhang
authors.affiliation: Department of Oncology, People's Hospital of Laiwu City No. 1 Xuehu Street, Changshao Road, Laiwu, Shandong, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Department of Oncology, People's Hospital of Laiwu City No. 1 Xuehu Street, Changshao Road, Laiwu, Shandong, China.
authors.forename: Jiu De
authors.initials: JD
authors.lastname: Qi
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Soochow University Suzhou, Jiangsu Province, China.
authors.forename: Yi-Fu
authors.initials: YF
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, First Affiliated Hospital of Soochow University Suzhou, Jiangsu Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048429:Cell Size; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490895:GAB2 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Gab2; STAT3; invasion; non-small cell lung cancer