Mann 2019 Oncogene: Difference between revisions
No edit summary |
No edit summary |
||
Line 10: | Line 10: | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, nDNA;cell genetics | ||
|diseases=Cancer | |diseases=Cancer | ||
|injuries=Cell death | |injuries=Cell death |
Revision as of 14:43, 22 January 2019
Mann J, Githaka JM, Buckland TW, Yang N, Montpetit R, Patel N, Li L, Baksh S, Godbout R, Lemieux H, Goping IS (2019) Non-canonical BAD activity regulates breast cancer cell and tumor growth via 14-3-3 binding and mitochondrial metabolism. Oncogene [Epub ahead of print]. |
Mann J, Githaka JM, Buckland TW, Yang N, Montpetit R, Patel N, Li L, Baksh S, Godbout R, Lemieux H, Goping IS (2019) Oncogene
Abstract: The Bcl-2-associated death promoter BAD is a prognostic indicator for good clinical outcome of breast cancer patients; however, whether BAD affects breast cancer biology is unknown. Here we showed that BAD increased cell growth in breast cancer cells through two distinct mechanisms. Phosphorylation of BAD at S118 increased S99 phosphorylation, 14-3-3 binding and AKT activation to promote growth and survival. Through a second, more prominent pathway, BAD stimulated mitochondrial oxygen consumption in a novel manner that was downstream of substrate entry into the mitochondria. BAD stimulated complex I activity that facilitated enhanced cell growth and sensitized cells to apoptosis in response to complex I blockade. We propose that this dependence on oxidative metabolism generated large but nonaggressive cancers. This model identifies a non-canonical role for BAD and reconciles BAD-mediated tumor growth with favorable outcomes in BAD-high breast cancer patients.
โข Bioblast editor: Plangger M โข O2k-Network Lab: CA Edmonton Lemieux H
Labels: MiParea: Respiration, nDNA;cell genetics
Pathology: Cancer
Stress:Cell death
Organism: Human
Tissue;cell: Endothelial;epithelial;mesothelial cell
Preparation: Intact cells, Permeabilized cells
Enzyme: Complex I
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k
Labels, 2019-01