Nature cell biology, 2018-03, Vol.20 (3), p.272
2018
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Details
- Autor(en) / Beteiligte
- Titel
- RIPK1-mediated induction of mitophagy compromises the viability of extracellular-matrix-detached cells
- Ist Teil von
- Nature cell biology, 2018-03, Vol.20 (3), p.272
- Ort / Verlag
- England
- Erscheinungsjahr
- 2018
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- For cancer cells to survive during extracellular matrix (ECM) detachment, they must inhibit anoikis and rectify metabolic deficiencies that cause non-apoptotic cell death. Previous studies in ECM-detached cells have linked non-apoptotic cell death to reactive oxygen species (ROS) generation, although the mechanistic underpinnings of this link remain poorly defined. Here, we uncover a role for receptor-interacting protein kinase 1 (RIPK1) in the modulation of ROS and cell viability during ECM detachment. We find that RIPK1 activation during ECM detachment results in mitophagy induction through a mechanism dependent on the mitochondrial phosphatase PGAM5. As a consequence of mitophagy, ECM-detached cells experience diminished NADPH production in the mitochondria, and the subsequent elevation in ROS levels leads to non-apoptotic death. Furthermore, we find that antagonizing RIPK1/PGAM5 enhances tumour formation in vivo. Thus, RIPK1-mediated induction of mitophagy may be an efficacious target for therapeutics aimed at eliminating ECM-detached cancer cells.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1476-4679DOI: 10.1038/s41556-018-0034-2Titel-ID: cdi_pubmed_primary_29459781
- Format
- –
- Schlagworte
- Animals, Cell Adhesion, Cell Movement, Cell Proliferation, Cell Survival, Epithelial Cells - enzymology, Epithelial Cells - pathology, Extracellular Matrix - metabolism, Extracellular Matrix - pathology, Female, HCT116 Cells, HeLa Cells, Humans, Mammary Glands, Human - enzymology, Mammary Glands, Human - pathology, Mice, Nude, Mitochondria - enzymology, Mitochondria - pathology, Mitochondrial Degradation, Mitochondrial Proteins - genetics, Mitochondrial Proteins - metabolism, NADP - metabolism, Neoplasm Metastasis, Neoplasms - enzymology, Neoplasms - genetics, Neoplasms - pathology, Phosphoprotein Phosphatases - genetics, Phosphoprotein Phosphatases - metabolism, Reactive Oxygen Species - metabolism, Receptor-Interacting Protein Serine-Threonine Kinases - genetics, Receptor-Interacting Protein Serine-Threonine Kinases - metabolism, Signal Transduction, Tumor Burden