EGFR-rich extracellular vesicles derived from highly metastatic nasopharyngeal carcinoma cells accelerate tumour metastasis through PI3K/AKT pathway-suppressed ROS

Autor:	Junyu Huang, Chaoyi Li, Fei Li, Ting Xu, Xiner He, Jingyao Li, Mo Yang, Qing Zhang, Xin Zhao, Rui Sun, Nanyan Yang, Jinxin Ou
Rok vydání:	2020
Předmět:	0301 basic medicine Adult Male Histology Adolescent Cell Extracellular vesicles 03 medical and health sciences Extracellular Vesicles Phosphatidylinositol 3-Kinases 0302 clinical medicine otorhinolaryngologic diseases Medicine Humans Epidermal growth factor receptor Neoplasm Metastasis PI3K/AKT/mTOR pathway Research Articles Aged chemistry.chemical_classification reactive oxygen species Reactive oxygen species Nasopharyngeal Carcinoma biology business.industry Cancer Nasopharyngeal Neoplasms Cell Biology Middle Aged medicine.disease ErbB Receptors stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Nasopharyngeal carcinoma chemistry 030220 oncology & carcinogenesis Cancer research biology.protein Female business epidermal growth factor receptor Proto-Oncogene Proteins c-akt Intracellular Signal Transduction Research Article
Zdroj:	Journal of Extracellular Vesicles
ISSN:	2001-3078
Popis:	Nasopharyngeal carcinoma (NPC) is the most common cancer with high metastatic potential that occurs in the epithelial cells of the nasopharynx. Distant metastases are the primary cause for treatment failure and mortality of NPC patients. However, the underlying mechanism responsible for the initiation of tumour cell dissemination and tumour metastasis in NPC is not well understood. Here, we demonstrated that epidermal growth factor receptor (EGFR) was highly expressed in tumour tissues of NPC patients with distant metastases and was associated with a decrease in reactive oxygen species (ROS). We also revealed that extracellular vesicles (EVs) transfer occurred from highly to poorly metastatic NPC cells, mediating cell–cell communication and enhancing the metastatic potential of poorly metastatic NPC cells. Further experiments indicated that EVs derived from highly metastatic NPC cells induced the up‐regulation of EGFR and down‐regulation of ROS in low metastatic NPC cells. Mechanistically, EGFR‐rich EVs‐mediated EGFR overexpression down‐regulated intracellular ROS levels through the PI3K/AKT pathway, thus promoting the metastatic potential of poorly metastatic NPC cells. Strikingly, treatment with EVs secreted from highly metastatic NPC cells was significantly associated with rapid NPC progression and shorter survival in xenografted mice. These findings not only improve our understanding of EVs‐mediated NPC metastatic mechanism but also have important implications for the detection and treatment of NPC patients accompanied by aberrant EGFR‐rich EVs transmission.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f873907789b4a794322fe052b15425c https://pubmed.ncbi.nlm.nih.gov/33304472 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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