Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.

中文翻译：

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Migfilin 通过与 SNAP29 和 Vamp8 直接相互作用促进自噬通量。


自噬通过促进有害细胞成分的消除和营养物质的循环利用，在癌细胞的存活中发挥着至关重要的作用。了解自噬的分子调控对于开发癌症治疗的介入方法至关重要。在这项研究中，我们报道了migfilin（一种粘着斑蛋白）通过增加自噬体-溶酶体融合在促进自噬中发挥新作用。我们发现 migfilin 与 SNAP29 和 Vamp8 相关，从而促进 Stx17-SNAP29-Vamp8 SNARE 复合物的组装。 migfilin 的消耗会破坏 SNAP29 介导的 SNARE 复合物的形成，从而阻断自噬体-溶酶体融合，最终抑制癌细胞生长。 SNARE 复合体形成的恢复挽救了米格菲林缺乏引起的自噬流缺陷。最后，我们发现米格非林的消耗抑制了癌细胞的增殖。 SNARE 复合物重新组装成功逆转了 migfilin 缺陷诱导的癌细胞生长抑制。总而言之，我们的研究揭示了 migfilin 作为自噬调节蛋白的新功能，并表明靶向 migfilin-SNARE 组装体可以提供一种有前景的治疗方法来缓解癌症进展。