Insight into the role of Wnt5a-induced signaling in normal and cancer cells.

Wnt5a is involved in the activation of noncanonical Wnt signaling, including planar cell polarity (PCP) and Wnt-Ca(2+) pathways. The Ror-family of receptor tyrosine kinases is composed of Ror1 and Ror2 in mammals. Ror2 acts as a receptor or coreceptor for Wnt5a and regulates Wnt5a-induced activation of PCP pathway, and Wnt5a-Ror2 axis indeed plays critical roles in the developmental morphogenesis by regulating cell polarity and migration. Furthermore, Wnt5a-Ror2 axis is constitutively activated in cancer cells and confers highly motile and invasive properties on cancer cells through the expression of matrix metalloproteinase genes and enhanced formation of invadopodia. Meanwhile, Wnt5a also exhibits a tumor-suppressive function in certain cancers, including breast and colorectal carcinomas. Thus, it is of great importance to understand the respective molecular mechanisms governing Wnt5a-mediated tumor-progressive and tumor-suppressive functions, in order to develop novel and proper diagnostic and therapeutic strategies targeting Wnt5a signaling for human cancers.