MAP3K9 and neoplasm: RNA sequencing reveals upregulation of MLKs in drug-resistant tumor specimens and biochemical assays have also shown that catalytic activity of MLK1, -2, -3, and/or -4 is required for direct phosphorylation of MEK, in a Raf-independent manner, leading to reactivation of ERK signaling and decreased sensitivity to the B-Raf inhibitor [13].