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Rasal2 suppresses breast cancer cell proliferation modulated by secretory autophagy

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Abstract

Rasal2, a Ras-GTPase-activating protein (RasGAP), is a tumor suppressor in Luminal B breast cancer, frequently metastatic and recurrent. Exosomes (Exos) are small membrane vesicles secreted by various cell types, including tumor cells, recognized as vehicles for cell-to-cell communication. Our study aimed to investigate whether Rasal2 regulates breast cancer cell growth via affecting this process. In this paper, we described that Rasal2 knockout (KO) in MCF-7 cells enhanced exosomal release and increased autophagy-related proteins in exosomal fraction, while attenuated by exosome release inhibitor GW4869. Moreover, MCF-7 cells with chloroquine (CQ) treatment boosted Rasal2 KO-induced secretory autophagy. In addition, we presented that exosomes derived from KO MCF-7 cells (KO-exo) significantly promoted breast cancer cell proliferation compared to those from MCF-7 cells transfected with an empty crispr-cas9 plasmid serving as controls (sgNT-exo); however, exosomes purified from KO MCF-7 cells co-cultured with 3-methyladenine ((3-MA + KO)-exo)/CQ ((CQ + KO)-exo) dramatically inhibited/facilitated MCF-7 cell proliferation in contrast to KO-exo group, separately. In conclusion, our findings revealed a new mechanism of Rasal2 in the regulation of breast cancer cell proliferation via autophagy-exo-mediated pathway.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81874146 to YY).

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Authors and Affiliations

  1. Department of Pharmacology and Biochemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China

    Xuan Wang & Yonghua Yang

  2. Department of Tumor Medical Information, Astrazeneca, Shanghai, 201203, China

    Xuzhi Yin

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  1. Xuan Wang
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  2. Xuzhi Yin
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  3. Yonghua Yang
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Correspondence to Yonghua Yang.

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Wang, X., Yin, X. & Yang, Y. Rasal2 suppresses breast cancer cell proliferation modulated by secretory autophagy. Mol Cell Biochem 462, 115–122 (2019). https://doi.org/10.1007/s11010-019-03615-7

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