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Molecular and Cellular Biochemistry

, Volume 462, Issue 1–2, pp 115–122 | Cite as

Rasal2 suppresses breast cancer cell proliferation modulated by secretory autophagy

  • Xuan Wang
  • Xuzhi Yin
  • Yonghua YangEmail author
Article
  • 320 Downloads

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.

Graphic abstract

Keywords

Breast cancer Rasal2 Exosomal release Secretory autophagy Cell proliferation 

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology and Biochemistry, School of PharmacyFudan UniversityShanghaiChina
  2. 2.Department of Tumor Medical InformationAstrazenecaShanghaiChina

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