MAP2K1 and cancer: Signaling through mitogen-activated protein kinase (MAPK or pERK1/2) is crucial to cancer cell proliferation and differentiation16 and inflammatory cytokine production via the RAS-RAF-MEK-ERK1/2 cascade.17 With respect to the downstream effects of MAPK signaling on bone remodeling, previous studies have shown that [1] proinflammatory states are osteoclastogenic,18 [2] MEK inhibitors enhance osteoblastic differentiation,19 although constitutive activation of MEK-1 hinders osteoblastic differentiation,20 and [3] ERK1/2 inactivation significantly reduces osteoblast RANKL expression.21