The involvement of noncanonical Wnt signaling in cancers

Abstract Wnt signaling is one of the key cascades regulating normal tissue development and has been tightly associated with cancer. The Wnt signaling can be subdivided into two categories: canonical & noncanonical. Noncanonical Wnt signaling pathways mainly include Wnt/PCP (planar cell polarity) signaling and Wnt-cGMP (cyclic guanosine monophosphate) /Ca2+ signaling. It has been well studied by previous researches that noncanonical Wnt signaling regulates multiple cell functions including proliferation, differentiation, adhesion, polarity, motility, and migration. The aberrant activation or inhibition of noncanonical Wnt signaling is crucial in cancer progression, exerting both oncogenic and tumor-suppressive effects. Recent studies show the involvement of noncanonical Wnt in regulating cancer cell invasion, metastasis, metabolism, and inflammation. Here, we review current insights into novel components of non-canonical signalings and describe their involvement in various cancer types. We also summarize recent biological and clinical discoveries that outline non-canonical Wnt signaling in tumorigenesis. Finally, we provide an overview of current strategies to target non-canonical Wnt signaling in cancer and challenges that are associated with such approaches.