RAB7A-enriched extracellular vesicles drive early-metastasis and immune evasion in triple-negative breast cancer.
- 1Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Second Road, Shanghai 200025, China.
- 2School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong 999077, China.
Abstract
Early-metastatic triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and responds poorly to immunotherapy. However, mechanisms of metastasis or immune evasion remain incompletely understood. This study demonstrates that tumor-derived small extracellular vesicles (sEV) from a clinical cohort of 16 TNBC patients promote cytoskeletal remodeling, tumor growth, and lung metastasis. Label-free quantitative proteomic analysis revealed that RAB7A is enriched in sEVs from early-metastatic patients, whereas other endolysosomal proteins were not markedly altered. Mechanistically, sEV-delivered RAB7A activated the MAPK/ERK signaling pathway, thereby promoting paxillin phosphorylation, F-actin polymerization, and enhanced cell motility. Concurrently, RAB7A upregulated c-MYC expression which bound to the CD274 promoter and increased PD-L1 expression, contributing to immune evasion. Importantly, combined treatment with the RAB7A inhibitor CID1067700 and anti-PD-1 suppressed both tumor growth and metastasis, and enhanced intratumoral infiltration of CD8⁺ T cell. Collectively, this study found that the sEV/RAB7A/ERK axis promotes early metastasis and immune evasion in TNBC, and propose that targeting RAB7A-enriched sEV plus PD-1 blockade represents a mechanistically rational therapeutic strategy in aggressive TNBC.
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BibTeX
@article{zhong2026rab7aenriched,
title = {{RAB7A-enriched extracellular vesicles drive early-metastasis and immune evasion in triple-negative breast cancer.}},
author = {Hanyi Zhong and Han Wang and Weiqi Gao and Ziling Zhou and Shoutang Wang and Ou Huang and Renhong Huang and Zheng Wang and Kunwei Shen},
journal = {International journal of biological sciences},
year = {2026},
month = sep,
doi = {10.7150/ijbs.138205},
url = {https://europepmc.org/article/MED/42909978},
note = {CC BY},
}
RIS
TY - JOUR
TI - RAB7A-enriched extracellular vesicles drive early-metastasis and immune evasion in triple-negative breast cancer.
AU - Hanyi Zhong
AU - Han Wang
AU - Weiqi Gao
AU - Ziling Zhou
AU - Shoutang Wang
AU - Ou Huang
AU - Renhong Huang
AU - Zheng Wang
AU - Kunwei Shen
PY - 2026
DA - 2026/09/18
JO - International journal of biological sciences
DO - 10.7150/ijbs.138205
UR - https://europepmc.org/article/MED/42909978
AB - Early-metastatic triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer and responds poorly to immunotherapy. However, mechanisms of metastasis or immune evasion remain incompletely understood. This study demonstrates that tumor-derived small extracellular vesicles (sEV) from a clinical cohort of 16 TNBC patients promote cytoskeletal remodeling, tumor growth, and lung metastasis. Label-free quantitative proteomic analysis revealed that RAB7A is enriched in sEVs from early-metastatic patients, whereas other endolysosomal proteins were not markedly altered. Mechanistically, sEV-delivered RAB7A activated the MAPK/ERK signaling pathway, thereby promoting paxillin phosphorylation, F-actin polymerization, and enhanced cell motility. Concurrently, RAB7A upregulated c-MYC expression which bound to the CD274 promoter and increased PD-L1 expression, contributing to immune evasion. Importantly, combined treatment with the RAB7A inhibitor CID1067700 and anti-PD-1 suppressed both tumor growth and metastasis, and enhanced intratumoral infiltration of CD8⁺ T cell. Collectively, this study found that the sEV/RAB7A/ERK axis promotes early metastasis and immune evasion in TNBC, and propose that targeting RAB7A-enriched sEV plus PD-1 blockade represents a mechanistically rational therapeutic strategy in aggressive TNBC.
SN - 1449-2288
ER -