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

Abstract 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 i...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Publishing Group 2023-08-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-023-06007-4
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author 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
author_facet 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
author_sort Jun-qi Luo
collection DOAJ
description Abstract 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.
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spelling doaj.art-c40cdfb1f8c1429c81f4f0cb00bcf9e32023-08-06T11:26:03ZengNature Publishing GroupCell Death and Disease2041-48892023-08-0114811410.1038/s41419-023-06007-4Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1Jun-qi Luo0Tao-wei Yang1Jun Wu2Hou-hua Lai3Li-bin Zou4Wen-bin Chen5Xu-min Zhou6Dao-jun Lv7Sheng-ren Cen8Zi-ning Long9Yi-you Mao10Peng-xiang Zheng11Xiao-hong Su12Zhi-yong Xian13Fang-peng Shu14Xiang-ming Mao15Department of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityDepartment of Urology, Guangdong Provincial People’s Hospital’s Nanhai HospitalDepartment of Urology, Guangzhou Women and Children’s Medical Center, National Children’s Medical Center for South Central Region, Guangzhou Medical UniversityDepartment of Urology, Zhujiang Hospital, Southern Medical UniversityAbstract 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.https://doi.org/10.1038/s41419-023-06007-4
spellingShingle 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
Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1
Cell Death and Disease
title Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1
title_full Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1
title_fullStr Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1
title_full_unstemmed Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1
title_short Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1
title_sort exosomal pgam1 promotes prostate cancer angiogenesis and metastasis by interacting with actg1
url https://doi.org/10.1038/s41419-023-06007-4
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