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Dysregulation of mitochondrial dynamics proteins are a targetable feature of human tumors

Anderson, Gray R ; Wardell, Suzanne E ; Cakir, Merve ; Yip, Catherine ; Ahn, Yeong-Ran ; Ali, Moiez ; Yllanes, Alexander P ; Chao, Christina A ; McDonnell, Donald P ; Wood, Kris C

Nature communications, 2018-04, Vol.9 (1), p.1677-13, Article 1677 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Dysregulation of mitochondrial dynamics proteins are a targetable feature of human tumors
Autor: Anderson, Gray R ; Wardell, Suzanne E ; Cakir, Merve ; Yip, Catherine ; Ahn, Yeong-Ran ; Ali, Moiez ; Yllanes, Alexander P ; Chao, Christina A ; McDonnell, Donald P ; Wood, Kris C
Assuntos: Animals ; Antineoplastic Agents - administration & dosage ; Apoptosis ; Biomarkers ; Cancer ; Cell Line, Tumor ; Cellular structure ; DIABLO protein ; Dynamics ; Female ; Humans ; Mice ; Mice, Nude ; Mitochondria ; Mitochondria - genetics ; Mitochondria - metabolism ; Mitochondrial DNA ; Mitochondrial Dynamics ; Mitochondrial Proteins - genetics ; Mitochondrial Proteins - metabolism ; Neoplasms - drug therapy ; Neoplasms - genetics ; Neoplasms - metabolism ; Organelles ; Perturbation ; Pharmacology ; Proteins ; Sensitivity ; Tumor cell lines ; Tumors
É parte de: Nature communications, 2018-04, Vol.9 (1), p.1677-13, Article 1677
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SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Altered mitochondrial dynamics can broadly impact tumor cell physiology. Using genetic and pharmacological profiling of cancer cell lines and human tumors, we here establish that perturbations to the mitochondrial dynamics network also result in specific therapeutic vulnerabilities. In particular, through distinct mechanisms, tumors with increased mitochondrial fragmentation or connectivity are hypersensitive to SMAC mimetics, a class of compounds that induce apoptosis through inhibition of IAPs and for which robust sensitivity biomarkers remain to be identified. Further, because driver oncogenes exert dominant control over mitochondrial dynamics, oncogene-targeted therapies can be used to sensitize tumors to SMAC mimetics via their effects on fission/fusion dynamics. Collectively, these data demonstrate that perturbations to the mitochondrial dynamics network induce targetable vulnerabilities across diverse human tumors and, more broadly, suggest that the altered structures, activities, and trafficking of cellular organelles may facilitate additional cancer therapeutic opportunities.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Dysregulation of mitochondrial dynamics proteins are a targetable feature of human tumors

Anderson, Gray R ; Wardell, Suzanne E ; Cakir, Merve ; Yip, Catherine ; Ahn, Yeong-Ran ; Ali, Moiez ; Yllanes, Alexander P ; Chao, Christina A ; McDonnell, Donald P ; Wood, Kris C

England: Nature Publishing Group

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