研究动态
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外泌体中的PGAM1与ACTG1相互作用,促进前列腺癌的血管生成和转移。

Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1.

发表日期:2023 Aug 04
作者: Jun-Qi Luo, Tao-Wei Yang, Jun Wu, Hou-Hua Lai, Li-Bin Zou, Wen-Bin Chen, Xu-Min Zhou, Dao-Jun Lv, Sheng-Ren Cen, Zi-Ning Long, Yi-You Mao, Peng-Xiang Zheng, Xiao-Hong Su, Zhi-Yong Xian, Fang-Peng Shu, Xiang-Ming Mao
来源: Cell Death & Disease

摘要:

肿瘤来源的外泌体及其含量促进了癌症转移。 磷酸甘油酸变异酶1(PGAM1)参与了各种与癌症相关的过程。尽管如此,外泌体PGAM1在前列腺癌(PCa)转移中的潜在机制仍不清楚。在本研究中,我们进行了体外和体内实验,以确定外泌体PGAM1在转移性PCa患者血管生成中的功能。我们进行了谷胱甘肽-S-转移酶拉取、共免疫沉淀、蛋白印迹和明胶降解实验,以确定外泌体PGAM1在PCa中的作用途径。我们的结果显示,与非转移性PCa患者相比,转移性PCa患者的血浆中外泌体PGAM1水平显著增加。此外,PGAM1通过促进浸润足形成来成为促进PCa细胞转移的关键因子,并可由PCa细胞的外泌体传递给人脐静脉内皮细胞(HUVECs)。另外,外泌体PGAM1能够结合γ-肌动蛋白(ACTG1),该蛋白促进HUVECs中的成髓体形成和新生血管出芽。体内实验结果显示,外泌体PGAM1通过尾静脉注射PCa细胞增强裸鼠的肺转移。总之,外泌体PGAM1促进了血管生成,并可用作PCa转移的液体活检标记物。©2023作者。
Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis.© 2023. The Author(s).