Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exoso...

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Bibliographic Details
Published in:Clinical & experimental metastasis 2023-02, Vol.40 (1), p.105-116
Main Authors: Liu, Xin, Li, Yue, Chen, Chunjing, Dong, Jiyang, Zhou, Jie, Tong, Dandan, Wang, Lei, Gao, Xiang, Kang, Xinmei
Format: Article
Language:English
Subjects:
Acids
Animals
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cell Line, Tumor
Cells
Endothelial Cells
EphA2 protein
Exosomes
Gene expression
Hematology
Humans
Kinases
Laboratories
Medicine
Metastases
Metastasis
Mice
MicroRNAs - metabolism
Neoplasm Metastasis
Oncology
Permeability
Protein-tyrosine kinase
Proteins
Research Paper
Surgical Oncology
Therapeutic targets
Triple Negative Breast Neoplasms
Tyrosine
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Summary:Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.
ISSN:0262-0898
1573-7276
DOI:10.1007/s10585-022-10194-3