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...
Main Authors: | , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Nature Publishing Group
2023-08-01
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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. |
first_indexed | 2024-03-12T17:06:27Z |
format | Article |
id | doaj.art-c40cdfb1f8c1429c81f4f0cb00bcf9e3 |
institution | Directory Open Access Journal |
issn | 2041-4889 |
language | English |
last_indexed | 2024-03-12T17:06:27Z |
publishDate | 2023-08-01 |
publisher | Nature Publishing Group |
record_format | Article |
series | Cell Death and Disease |
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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