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.
Gab1 SDF-1 Human chondrosarcoma Apoptosis
This is a preview of subscription content, log in to check access
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.
Azzi G, Velez M, Mathias-Machado MC. Isocitrate dehydrogenase mutations in chondrosarcoma: the crossroads between cellular metabolism and oncogenesis. Curr Opin Oncol. 2014;26:403–7.CrossRefPubMedGoogle Scholar
DeLaney TF, Liebsch NJ, Pedlow FX, et al. Long-term results of phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol. 2014;110:115–22.CrossRefPubMedGoogle Scholar
Frezza AM, Cesari M, Baumhoer D, et al. Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. Eur J Cancer. 2015;51:374–81.CrossRefPubMedGoogle Scholar
Yamasaki S, Nishida K, Yoshida Y, et al. Gab1 is required for EGF receptor signaling and the transformation by activated ErbB2. Oncogene. 2003;22:1546–56.CrossRefPubMedGoogle Scholar
Gillgrass A, Cardiff RD, Sharan N, et al. Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression. Oncogene. 2003;22:9151–5.CrossRefPubMedGoogle Scholar
Seiden-Long I, Navab R, Shih W, et al. Gab1 but not Grb2mediates tumor progression in Met overexpressing colorectal cancer cells. Carcinogenesis. 2008;29:647–55.CrossRefPubMedGoogle Scholar