News - 09/14/2016 - 1:14pm

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Puigserver Lab connects mitochondrial heterogeneity to metastasis
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Metabolic reprogramming in cancer cells is tightly associated with tumor progression but the effect of metabolic regulatory circuits on metastasis processes is poorly understood. New work from the Puigserver lab, published in Nature, reports that mitochondrial heterogeneity driven through the transcriptional coactivator PGC1a defines populations of melanoma cells with different metastatic capacity. Mechanistically, a PGC1a transcriptional axis suppresses a subset of integrin genes that are known to influence invasion and metastasis. This axis is the target of BRAF inhibitors that independently of its cytostastic effects suppress metastasis through integrin signaling. Thus, PGC1a -mediated mitochondrial heterogeneity is important during melanoma progression changing in response to different signals including nutrients, and switching between survival-proliferation and invasion-metastasis.