The Rab protein family is composed of small GTP-binding proteins involved in intracellular vesicle trafficking. In particular, Rab3a which is one of four Rab3 proteins (a, b, c, and d isoforms) is associated with synaptic vesicle trafficking in normal brain. However, despite the elevated level of Rab3a in tumors, its role remains unclear. Here we report a tumorigenic role of Rab3a in brain tumors. Elevated level of Rab3a expression in human was confirmed in both glioma cell lines and glioblastoma multiforme patient specimens. Ectopic Rab3a expression in glioma cell lines and primary astrocytes promoted cell proliferation by increasing cyclin D1 expression, induced resistance to anti-cancer drug and irradiation, and accelerated foci formation in soft agar and tumor formation in nude mice. The overexpression of Rab3a augmented the tumorsphere-forming ability of glioma cells and p53−/− astrocytes and increased expression levels of various stem cell markers. Taken together, our results indicate that Rab3a is a novel oncogene involved in glioma initiation and progression.
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This work was supported by the National Research Foundation of Korea (NRF) Grants funded by the Korea government (MSIP) (No. NRF-2009-0070325 to S.C. Kim and No. 2013M2A2A7042530 to H. Kim) and Hallym University Research Fund (HRF-G-2012-4, to S.C. Kim).
Jun-Kyum Kim and Seung-Yup Lee have contributed equally to this work.
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Kim, JK., Lee, SY., Park, CW. et al. Rab3a promotes brain tumor initiation and progression. Mol Biol Rep 41, 5903–5911 (2014). https://doi.org/10.1007/s11033-014-3465-2
- Glioblastoma multiforme
- Cyclin D1
- Drug resistance