YAP‑mediated crosstalk between the Wnt and Hippo signaling pathways (Review

Abstract

Yes-associated protein (YaP) acts as a transcriptional co-activator in gene expression and cell proliferation control by binding to the transcriptional factor Tea domain (Tead) of the Hippo signaling pathway in the nucleus, and also acts as a regulator by binding to another transcriptional co-activator, β-catenin of the Wnt signaling pathway. Whether YaP preferentially acts as a transcriptional co-regulator of the activity of the Hippo signaling pathway or as a regulator in the Wnt signaling pathway depends on the cell type. nuclear YaP upregulates the expression of β-catenin, while cytoplasmic YaP has a negative effect on this expression. The present mini-review focused on the important roles of YaP and further discussed the cross-links between the Wnt and Hippo signaling pathways. The Wnt and Hippo signaling pathways are both related to the development of fibrosis or cancer. The current review discussed treatment approaches for these conditions based on the two pathways. YaP, the intersection of these two signaling pathways, has the potential to be developed as a novel treatment target, according to previous basic studies on fibroblasts and cancer cells. Contents1. introduction 2. YaP complex in the Hippo and Wnt signaling pathway 3. YaP serves a key role in controlling organ size 4. YaP is a transcriptional co-activator or a regulator depending on the cell type 5. YAP has both negative and positive influences on the Wnt signaling pathway 6. inspiration of new routes for future treatment 7. conclusion

Crosstalk of Cancer Signaling Pathways by Cyclic Hexapeptides and Anthraquinones from Rubia cordifolia

“…A recent review on YAP describes its crosstalk between Hippo and Wnt pathways. YAP preferentially acts as a transcriptional co-regulator of Hippo signaling pathway or as a regulator in the Wnt signaling pathway depending on the cell type [32]. The inhibition of YAP by RA-V, as demonstrated by Ji et al, could be responsible for the Wnt inhibition observed from our study.…”

“…The crosstalk between cancer signaling pathways plays several complex roles in cancer and the identifying targets modulating these pathways serve as the current focus on the cancer treatment approach. Among them, the Wnt signaling pathway is known for its involvement in cancer initiation and progression via the activation of β-catenin signaling [32]. It has been reported that the cytoplasmic YAP is involved in regulating the tissue differentiation and migration of tumor cells by binding to β-catenin [36].…”

Yes-Associated Protein Is Required for ZO-1-Mediated Tight-Junction Integrity and Cell Migration in E-Cadherin-Restored AGS Gastric Cancer Cells

“…The E-cadherin-mediated AJ structure in the cell membrane sequestrates β-catenin, a key component of Wnt signaling, inhibiting Wnt signaling [ 37 ]. In addition, β-catenin binds to YAP and regulates its activity by sequestrating YAP in the cytoplasm [ 16 ], inhibiting malignant transformation. Therefore, reduction of Wnt signaling and YAP activity in EC96 cells is unsurprising.…”

“…Knockdown of β-catenin in densely cultured MCF10A cells decreases phosphorylation of the S127 residue of YAP and its nuclear accumulation [ 15 ]. β-catenin, a major effector of the Wnt signaling pathway and a component of AJs, binds with YAP directly and mediates cross-regulation between the Hippo and Wnt signaling pathways, regulating cell phenotypes including proliferation [ 16 ]. Several components of TJs regulate Hippo and YAP activities [ 12 ].…”

Emerging trends in colorectal cancer: Dysregulated signaling pathways (Review)

“…The APc/axin/GSK3β complex from the Wnt/β-catenin pathway and SMAd7 can alter the function of SMAd proteins of the TGF-β pathway, resulting in delayed apoptosis and metastasis, and an increased cell growth and division. Studies have indicated that the dsh protein of the Wnt pathway influences the translocation of YAP protein (Hippo pathway) by close contact inhibition of E-cadherin (238,239).…”