Chloride intracellular channel 3: A secreted pro-invasive oxidoreductase
| Autor: | Sara Zanivan, Jim C. Norman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteomics Proteome Angiogenesis Extracellular matrix chemistry.chemical_compound angiogenesis stiffness 0302 clinical medicine Cancer-Associated Fibroblasts Neoplasms CAF oxidoreductase chemistry.chemical_classification biology Neovascularization Pathologic CLIC3 invasion Glutathione Cell biology Extracellular Matrix Treatment Outcome Disease Progression TGM2 Female Oxidoreductases Oxidation-Reduction Protein Binding integrin Integrin Mice Nude Editorials: Cell Cycle Features Models Biological Article 03 medical and health sciences Oxidoreductase Chloride Channels GTP-Binding Proteins Cell Line Tumor Human Umbilical Vein Endothelial Cells cancer Animals Humans Neoplasm Invasiveness Protein Glutamine gamma Glutamyltransferase 2 Molecular Biology Transglutaminases Biological Transport Cell Biology Molecular biology Survival Analysis Mice Inbred C57BL Chloride intracellular channel 3 secretome 030104 developmental biology chemistry Cell culture biology.protein 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Cell Cycle Nature Communications |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion. The secretome from cancer and stromal cells contributes to the creation of a microenvironment, which in turn contributes to invasion and angiogenesis. Here, the authors compare the secretomes of immortalized normal fibroblasts and cancer-derived fibroblast and identify CLIC3 as a driver of cancer progression. |
| Databáze: | OpenAIRE |
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