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.

中文翻译：

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Rasal2 抑制由分泌性自噬调节的乳腺癌细胞增殖。

Rasal2 是一种 Ras-GTPase 激活蛋白 (RasGAP)，是 Luminal B 乳腺癌中的一种肿瘤抑制因子，经常转移和复发。外泌体 (Exos) 是由各种细胞类型（包括肿瘤细胞）分泌的小膜囊泡，被认为是细胞间通讯的载体。我们的研究旨在调查 Rasal2 是否通过影响这一过程来调节乳腺癌细胞的生长。在本文中，我们描述了 MCF-7 细胞中的 Rasal2 敲除 (KO) 增强了外泌体释放并增加了外泌体部分中的自噬相关蛋白，同时被外泌体释放抑制剂 GW4869 减弱。此外，氯喹 (CQ) 处理的 MCF-7 细胞增强了 Rasal2 KO 诱导的分泌性自噬。此外，我们提出，与用空的crispr-cas9质粒转染的MCF-7细胞（sgNT-exo）相比，源自KO MCF-7细胞（KO-exo）的外泌体显着促进乳腺癌细胞增殖；然而，与 3-甲基腺嘌呤 ((3-MA + KO)-exo)/CQ ((CQ + KO)-exo) 共培养的 KO MCF-7 细胞纯化的外泌体显着抑制/促进 MCF-7 细胞增殖分别到 KO-exo 组。总之，我们的研究结果揭示了Rasal2通过自噬-exo介导的途径调节乳腺癌细胞增殖的新机制。与 KO 相比，从与 3-甲基腺嘌呤 ((3-MA + KO)-exo)/CQ ((CQ + KO)-exo) 共培养的 KO MCF-7 细胞中纯化的外泌体显着抑制/促进 MCF-7 细胞增殖-exo 组，分别。总之，我们的研究结果揭示了Rasal2通过自噬-exo介导的途径调节乳腺癌细胞增殖的新机制。与 KO 相比，从与 3-甲基腺嘌呤 ((3-MA + KO)-exo)/CQ ((CQ + KO)-exo) 共培养的 KO MCF-7 细胞中纯化的外泌体显着抑制/促进 MCF-7 细胞增殖-exo 组，分别。总之，我们的研究结果揭示了Rasal2通过自噬-exo介导的途径调节乳腺癌细胞增殖的新机制。