title: GIT1 promotes lung cancer cell metastasis through modulating Rac1/Cdc42 activity and is associated with poor prognosis.
abstract: G-protein-coupled receptor kinase interacting protein 1 (GIT1) is participated in cell movement activation, which is a fundamental process during tissue development and cancer progression. GIT1/PIX forming a functional protein complex that contributes to Rac1/Cdc42 activation, resulting in increasing cell mobility. Although the importance of Rac1/Cdc42 activation is well documented in cancer aggressiveness, the clinical importance of GIT1 remains largely unknown. Here, we investigated the clinical significance of GIT1 expression in non-small-cell lung cancer (NSCLC) and also verified the importance of GIT1-Rac1/Cdc42 axis in stimulating NSCLC cell mobility. The result indicated higher GIT1 expression patients had significantly poorer prognoses in disease-free survival (DFS) and overall survival (OS) compared with lower GIT1 expression patients. Higher GIT1 expression was an independent prognostic factor by multivariate analysis and associated with migration/invasion of NSCLC cells in transwell assay. In vivo studies indicated that GIT1 promotes metastasis of NSCLC cells. Finally, GIT1 was found to stimulate migration/invasion by altering the activity of Rac1/Cdc42 in NSCLC cells. Together, the GIT1 expression is associated with poor prognosis in patients with NSCLC. GIT1 is critical for the invasiveness of NSCLC cells through stimulating the activity of Rac1/Cdc42.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.|Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jeng-Shou
authors.initials: JS
authors.lastname: Chang
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Su
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Graduate School of Biomedical Sciences, The University of Texas Houston Health Science Center, Houston, Texas, USA.
authors.forename: Wen-Hsuan
authors.initials: WH
authors.lastname: Yu
authors.affiliation: Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Institute of Genomic Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Tsung-Ching
authors.initials: TC
authors.lastname: Lai
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Jan
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Shen
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jin-Yuh
authors.initials: JY
authors.lastname: Shew
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Jean
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Institute of Biochemical Science, National Taiwan University College of Life Science, Taipei, Taiwan.
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.affiliation: Medical Biology, Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D015398:Signal Transduction; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; C107953:RAC1 protein, human; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
keywords: GIT1; Rac1/Cdc42; Rho GTPases; lung cancer prognosis; metastasis