Back to Search
Start Over
Small Extracellular Vesicle Regulation of Mitochondrial Dynamics Reprograms a Hypoxic Tumor Microenvironment.
- Source :
-
Developmental cell [Dev Cell] 2020 Oct 26; Vol. 55 (2), pp. 163-177.e6. Date of Electronic Publication: 2020 Aug 10. - Publication Year :
- 2020
-
Abstract
- The crosstalk between tumor cells and the adjacent normal epithelium contributes to cancer progression, but its regulators have remained elusive. Here, we show that breast cancer cells maintained in hypoxia release small extracellular vesicles (sEVs) that activate mitochondrial dynamics, stimulate mitochondrial movements, and promote organelle accumulation at the cortical cytoskeleton in normal mammary epithelial cells. This results in AKT serine/threonine kinase (Akt) activation, membrane focal adhesion turnover, and increased epithelial cell migration. RNA sequencing profiling identified integrin-linked kinase (ILK) as the most upregulated pathway in sEV-treated epithelial cells, and genetic or pharmacologic targeting of ILK reversed mitochondrial reprogramming and suppressed sEV-induced cell movements. In a three-dimensional (3D) model of mammary gland morphogenesis, sEV treatment induced hallmarks of malignant transformation, with deregulated cell death and/or cell proliferation, loss of apical-basal polarity, and appearance of epithelial-to-mesenchymal transition (EMT) markers. Therefore, sEVs released by hypoxic breast cancer cells reprogram mitochondrial dynamics and induce oncogenic changes in a normal mammary epithelium.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Cell Movement physiology
Cell Proliferation physiology
Epithelial Cells metabolism
Humans
Mammary Glands, Human metabolism
Protein Serine-Threonine Kinases metabolism
Cell Transformation, Neoplastic pathology
Epithelial-Mesenchymal Transition physiology
Mitochondrial Dynamics physiology
Tumor Microenvironment physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 55
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 32780991
- Full Text :
- https://doi.org/10.1016/j.devcel.2020.07.014