Abstract
Wnt5a is one of the potent signaling molecules that initiates responses involved in cancer through activation of both canonical and noncanonical signaling cascades. Wnt5a both directly and indirectly triggers cancer-associated signaling pathways based on the cancer type. In colorectal cancer (CRC), altering Wnt5a expression can influence several cellular processes of tumor cells, including proliferation, differentiation, migration, invasion, and metastasis. This review summarizes the molecular mechanisms and clinical importance of Wnt5a in the pathogenesis of CRC for better understanding the pathogenesis and its potential role as a prognostic marker and as an appropriate therapeutic target in the treatment of this disease in the future.
Highlights
Wnt ligands are a large family of glycoproteins that initiate their signaling functions through binding to a member transmembrane of G-protein-coupled frizzled (Fzd) receptor and eventually activation of scaffolding protein disheveled (Dvl) [1, 2]
Following binding Wnt ligands to the Fzd receptor, the destructive complex is inactivated, leading to translocation of β-catenin into the nucleus where it tightly binds to specific transcription factors such as T cell factor/lymphoid enhancer-binding factor (TCF/LEF) to stimulate expression of target genes involved in cell proliferation and differentiation [9, 10]
Tumor suppressor and oncogenic effects of Wnt5a noncanonical ligands have been shown to be mediated by targeting processes related to cellular senescence, cancer stem cells, chemotherapy resistance, tumor microenvironment cells, cancer-associated inflammation, epithelial-mesenchymal transition (EMT), metastasis, cell proliferation, cell invasion, and cell migration in a wide range of various cancer cell lines [34]
Summary
Wnt ligands are a large family of glycoproteins that initiate their signaling functions through binding to a member transmembrane of G-protein-coupled frizzled (Fzd) receptor and eventually activation of scaffolding protein disheveled (Dvl) [1, 2]. Wnt proteins are generally functionally divided into canonical and noncanonical Wnt ligands, regulating several intracellular processes, including proliferation, migration, differentiation, and polarity, regulating both canonical and noncanonical Wnt β-catenin signaling cascades [3, 4]
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