Wnt5a is upregulated in various types of human cancers.281,282 Meanwhile, Wnt5a activation of JNK is linked with cytoskeletal remodeling and cell motility in various cell systems.283–285 For example, in melanoma, Wnt5a is thought to directly affect cell motility and metastasis.286 In this view, CD146 may represent the prime target to develop more effective and less toxic therapies toward Wnt5a/CD146/JNK activation for meeting the challenges from tumor metastasis. The gene discussed is WNT5A; the disease is melanoma.