Cupric Needs: Copper Is Necessary for Oncogenic BRAF Signaling

Metal cations are essential co-factors for many enzymes. Genetic evidence in flies showed the importance of copper in ERK kinase signaling. Brady and colleagues took this research a step further by focusing on how copper contributes to signaling in mutant BRAF cancers, including melanoma. In melanoma, BRAF^V600E activates the MEK1 and MEK2 kinases, which in turn activate the ERK1 and ERK2 kinases, which stimulate the MAPK pathway and promote cancer. Disrupting BRAF or MEK signaling shuts this pathway off, resulting in clinical responses.

Using mice lacking the Ctr1 copper transporter, they showed that BRAF^V600E signaling to ERK is dependent on intact copper transport, because MEK requires copper for activity. Proliferation of melanoma cell li…