In osteosarcoma, the planar cell polarity-like (PCP) Wnt signaling pathway, which consisted of Ras homolog family member A (RhoA), mitogen-activated protein kinase kinase-4 (MKK4) and Jun N-terminal Kinase (JNK), was activated when DKK1 inhibited Wnt signaling, resulting in transcriptional activation of cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) and promotion of tumor progression (25). Here, MAP2K4 is linked to cancer.