Tumor Biology

, Volume 37, Issue 1, pp 1141–1149 | Cite as

Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma

  • Yongqian Fan
  • Fengjian Yang
  • Xuhai Cao
  • Cong Chen
  • Xuelin Zhang
  • Xu Zhang
  • Weilong Lin
  • Xiaofeng Wang
  • Chengwei Liang
Original Article

Abstract

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.

Keywords

Gab1 SDF-1 Human chondrosarcoma Apoptosis 

Notes

Acknowledgments

We thank all the patients who were willing to be recruited in this investigation. At the same time, we thank other members in our laboratory for valuable suggestions and writing.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yongqian Fan
    • 1
  • Fengjian Yang
    • 1
  • Xuhai Cao
    • 1
  • Cong Chen
    • 1
  • Xuelin Zhang
    • 1
  • Xu Zhang
    • 1
  • Weilong Lin
    • 1
  • Xiaofeng Wang
    • 2
  • Chengwei Liang
    • 1
  1. 1.Department of OrthopedicsHuadong Hospital Affiliated to Fudan UniversityShanghaiChina
  2. 2.Department of OrthopedicsZhongshan Hospital Affiliated to Fudan UniversityShanghaiChina

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