ERK is known to inhibit JNK via an induction of DUSP4 mRNA and protein expression, while inhibition of MEK-ERK signalling activates JNK-JUN signaling through inhibition of the DUSP4.22,23 The MAP3K1-MAP2K4-JNK cascade activates JUN, which in combination with FOS, forms the Activator Protein-1 (AP-1) transactivator complex that controls a number of cellular processes including differentiation, proliferation, and apoptosis.24 The significant number of MAP3K1 and MAP2K4 mutations in different types of cancers is still poorly understood due to their dual roles in cell survival and apoptosis. Here, MAP2K4 is linked to cancer.