Exocyst controls exosome biogenesis via Rab11a.
Exocyst controls exosome biogenesis via Rab11a.
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DOI：
10.1016/j.omtn.2021.12.023
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Bai S;Hou W;Yao Y;Meng J;Wei Y;Hu F;Hu X;Wu J;Zhang N;Xu R;Tian F;Wang B;Liao H;Du Y;Fang H;He W;Liu Y;Shen B;Du J
肿瘤细胞主动释放大量的外泌体，其关键地参与癌症生物学的调节，包括头颈癌（HNC）。外泌体的生物发生和释放是复杂和精细的过程，被认为是类似于外泌囊介导的囊泡递送的过程。通过分析HNC患者中外囊亚基的表达及其作用，我们旨在鉴定外囊及其在外泌体生物发生中的功能，并研究HNC细胞中外泌体转运调控的分子机制。我们观察到外泌囊在HNC细胞中高度表达，并且可以促进这些细胞中的外泌体分泌。此外，下调外囊表达通过减少外泌体分泌来抑制HN 4细胞增殖。有趣的是，免疫荧光和电子显微镜显示，多泡体（MVB）敲除后的外囊的积累。自噬是外泌体降解的主要途径，其不被MVB的这种细胞内积累激活，但是当在细胞饥饿条件下自噬被激活时，这些MVB被消耗。Rab 11 a是一个参与MVB融合的小GTbR，也与外囊相互作用。这些结果表明，外囊可以调节外泌体的生物合成，并参与肿瘤细胞的恶性行为。外泌体在头颈癌（HNC）的发生和发展中起作用;然而，其分泌的具体机制仍不清楚。我们发现多泡体通过与HNC中的Rab 11 a结合而被外囊转运到质膜上进行外泌体分泌。
Tumor cells actively release large quantities of exosomes, which pivotally participate in the regulation of cancer biology, including head and neck cancer (HNC). Exosome biogenesis and release are complex and elaborate processes that are considered to be similar to the process of exocyst-mediated vesicle delivery. By analyzing the expression of exocyst subunits and their role in patients with HNC, we aimed to identify exocyst and its functions in exosome biogenesis and investigate the molecular mechanisms underlying the regulation of exosome transport in HNC cells. We observed that exocysts were highly expressed in HNC cells and could promote exosome secretion in these cells. In addition, downregulation of exocyst expression inhibited HN4 cell proliferation by reducing exosome secretion. Interestingly, immunofluorescence and electron microscopy revealed the accumulation of multivesicular bodies (MVBs) after the knockdown of exocyst. Autophagy, the major pathway of exosome degradation, is not activated by this intracellular accumulation of MVBs, but these MVBs are consumed when autophagy is activated under the condition of cell starvation. Rab11a, a small GTPase that is involved in MVB fusion, also interacted with the exocyst. These findings suggest that the exocyst can regulate exosome biogenesis and participate in the malignant behavior of tumor cells. Exosomes play a role in the occurrence and development of head and neck cancer (HNC); however, the specific mechanism for their secretion remains unclear. We found that the multivesicular body gets transported to the plasma membrane for exosome secretion by exocyst via binding with Rab11a in HNC.
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