github link
Accession IconGSE58721

BRAF inhibition leads to oxidative phosphorylation and cellular senescence in human melanoma cells

Organism Icon Homo sapiens
Sample Icon 14 Downloadable Samples
Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Submitter Supplied Information

Description
Targeting components of the mitogen-activated protein kinase (MAPK) pathway prolongs survival of patients with advanced BRAFV600E melanomas but such an approach is not curative because of the rapid acquisition of numerous resistance mechanisms. Here we analyze melanoma cells that evade MAPK inhibitors by undergoing a senescence-like, slow-growth, phenotype, which leads to acquired resistance. The initial therapeutic response is characterized by an integrated stress response program, including stimulation of autophagic flux, activation of the endoplasmic reticulum machinery, and an enhanced ability of detoxifying reactive oxygen species. Reversibly senescent cells also exhibit an increase in mitochondrial genome copy number and a strong metabolic shift towards oxidative phosphorylation (OxPhos). Inducing mitochondrial dysfunction by co-targeting the MAPK pathway and mitochondrial Hsp90-directed protein folding with specific inhibitors prevented entry of cells into a reversibly senescent state, suppressed mitochondrial energy metabolism and augmented therapy response.
PubMed ID
Total Samples
14
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Disease
Disease stage
Cell line
Time
Processing Information
Additional Metadata
No rows found
Loading...