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 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.

Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches

“…Solid malignant tumors, such as PRAD, rely on a sufficient blood supply to support their growth, development, and spread ( 9 ). Recent studies have confirmed the role of exosomal PGAM1 in promoting PRAD angiogenesis, suggesting its potential as a diagnostic marker for PRAD metastasis ( 10 ). Interleukin-30 disrupts prostate cancer cross-talk with endothelial cells by enhancing angiogenesis ( 11 ).…”

Multiplexed Opto-Microfluidic Biosensing: Advanced Platform for Prostate Cancer Detection

“…Traditional clinical methodologies for detecting PCa biomarkers present several significant limitations including high costs, complexity, patient discomfort, and lengthy analysis times. These conventional clinical assessments primarily rely on the PSA blood test and biopsy, enabling techniques such as immunohistochemistry (IHC), − immunofluorescence (IF), − specific protein quantification through Western blotting, − ELISA, − and reverse transcription-polymerase chain reaction. − …”

Pan-Cancer Analysis of PGAM1 and Its Experimental Validation in Uveal Melanoma Progression

“…Besides its metabolic role, PGAM1 can also interact with α-smooth muscle actin (ACTA2) to enhance tumor growth and metastasis and overcome erlotinib resistance in non-small-cell lung cancer (NSCLC) [19]. Moreover, PGAM1 can promote prostate cancer (PCa) angiogenesis and metastasis by binding to γ-actin (ACTG1) [20]. Additionally, elevated PGAM1 expression correlates with clinical features such as tumor grade, lymph node metastasis, and pathological staging, serving as an independent risk factor affecting prognosis.…”