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

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Tumor Biology

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.

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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.

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Authors and Affiliations

  1. Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan An Road, Shanghai, 200040, China

    Yongqian Fan, Fengjian Yang, Xuhai Cao, Cong Chen, Xuelin Zhang, Xu Zhang, Weilong Lin & Chengwei Liang

  2. Department of Orthopedics, Zhongshan Hospital Affiliated to Fudan University, No. 136 Xue Yuan Road, Shanghai, 200032, China

    Xiaofeng Wang

Authors
  1. Yongqian Fan
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  2. Fengjian Yang
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  3. Xuhai Cao
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  4. Cong Chen
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  5. Xuelin Zhang
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  6. Xu Zhang
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  7. Weilong Lin
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  8. Xiaofeng Wang
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  9. Chengwei Liang
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Corresponding authors

Correspondence to Xiaofeng Wang or Chengwei Liang.

Additional information

Yongqian Fan, Fengjian Yang, and Xuhai Cao contributed equally to this work as co-first authors.

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Fan, Y., Yang, F., Cao, X. et al. Gab1 regulates SDF-1-induced progression via inhibition of apoptosis pathway induced by PI3K/AKT/Bcl-2/BAX pathway in human chondrosarcoma. Tumor Biol. 37, 1141–1149 (2016). https://doi.org/10.1007/s13277-015-3815-2

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  • DOI: https://doi.org/10.1007/s13277-015-3815-2

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