Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma.
In recent decades, the stromal cell-derived factor-l (SDF-1) and Gab1 have been investigated to be involved in oncogenesis. However, it is scarcely reported that SDF-1-Gab1 pathway mediates proliferation and apoptosis in human chondrosarcoma (CS). In this study, we assessed the expression of Gab1 in 90 CS solid tumors by immunohistochemistry, immunoblotting, and qRT-PCR, and then, some in vitro assays were also applied to CS cells treated with SDF-1. We observed that the overexpression of Gab1 was positively correlated with lung metastasis and recurrence, and acts as an independent prognostic factor for CS patients. Gab1 expression was up-regulated in response to SDF-1 stimulation in CS cell line JJ012, SW1353, L3252. Overexpression of Gab1 increased Bcl-2/BAX ratio to promote cell growth via PI3K/AKT. On the other hand, silencing of Gab1 accelerated apoptosis and repressed the growth of CS cells, which further caused the inhibition of G1/S phase transition and decreased invasion capacity in CS cell lines. In vivo assay identified that the knockdown of Gab1 interfered with the tumor mass formation. In conclusion, our data identified overexpression of Gab1 in CS tissues, and Gab1 can be recommended as a novel biomarker for diagnosis and prognosis in patients with CS. Additionally, PI3K/AKT/Bcl-2/BAX axis was involved in Gab1-induced CS progression, indicating Gab1 might act as a new target for the treatment of CS patients.
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Yongqian
Y
Fan
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Fengjian
F
Yang
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Xuhai
X
Cao
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Cong
C
Chen
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Xuelin
X
Zhang
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Xu
X
Zhang
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China.
Weilong
W
Lin
Department of Orthopedics, Zhongshan Hospital Affiliated to Fudan University, No. 136 Xue Yuan Road, Shanghai, 200032, China. shwangxiaofeng@163.com.
Xiaofeng
X
Wang
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China. liangcweish126@163.com.
Chengwei
C
Liang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000818:Animals; D017209:Apoptosis; D001859:Bone Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002813:Chondrosarcoma / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; C000595707:BCL2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C098587:GAB1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
Apoptosis; Gab1; Human chondrosarcoma; SDF-1