BRAF upregulates HMGCL through an octamer transcription factor, Oct-1, which leads to increased intracellular levels of the HMGCL product, acetoacetate, which selectively enhances the binding of the BRAF V600E, but not the BRAF wild-type to MEK1 in V600E-positive cancer cells, to promote the activation of MEK–ERK signaling and, therefore, tumor growth. This evidence concerns the gene HMGCL and cancer.