Rasal2 suppresses breast cancer cell proliferation modulated by secretory autophagy
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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.
KeywordsBreast cancer Rasal2 Exosomal release Secretory autophagy Cell proliferation
This work was supported by grants from the National Natural Science Foundation of China (No. 81874146 to YY).
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Conflict of interest
The authors declare no conflict of interest.
- 21.Garcia NA, Ontoria-Oviedo I, Gonzalez-King H et al (2015) Glucose starvation in cardiomyocytes enhances exosome secretion and promotes angiogenesis in endothelial cells. PLoS ONE 10:e138849Google Scholar
- 22.Hernandez-Garcia MS, Miranda-Ozuna J, Salazar-Villatoro L et al (2019) Biogenesis of autophagosome in trichomonas vaginalis during macroautophagy induced by rapamycin-treatment and iron or glucose starvation conditions. J Eukaryot Microbiol. https://doi.org/10.1111/jeu.12712 CrossRefPubMedGoogle Scholar