Figure 5.

Model of BRD4-bound super-enhancer defining a ‘PGC-1α high’ subgroup of proliferative melanoma cells. PGC-1α suppresses the metastatic character of melanoma cells (PGC-1α high vs PGC-1α low), while promoting mitochondria biogenesis and protecting from oxidative stress. Pharmacological blockade of PGC-1α expression by BET inhibition leads to downstream loss of mitochondrial function and reduced OXPHOS, ultimately resulting in impaired cell proliferation. This does not induce WNT, TGF-β and integrin pathway activity,³³ which could otherwise promote a switch from a proliferative to an invasive phenotype.