Wnt/β-catenin signaling in cancers and targeted therapies

Yu, Fanyuan; Chen, Yu; Li, Feifei; Zuo, Yanqin; Wang, Yitian; Lin, Yu; Wu, Chenzhou; Wang, Chenglin; Ye, Ling

doi:10.1038/s41392-021-00701-5

Cited by 285 publications

(205 citation statements)

References 455 publications

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“…After reducing the expression level of circPVT1 in PTC cells, the ability of cell proliferation, migration, and invasion were significantly inhibited, and the Wnt/β-catenin signaling pathway was also inhibited. The Wnt/β-catenin signaling pathway, also known as the classic Wnt signaling pathway, has been studied in-depth [ 51 , 52 ]. Activation of the classic Wnt signaling pathway can contribute to extracellular Wnt combining with the transmembrane receptors LRP5/6 and Fzd to form a complex.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

Zeng¹,

Yuan²,

Zhou³

et al. 2021

Bioengineered

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Circular RNAs (circRNAs) have been reported to be involved in the progression of papillary thyroid carcinoma (PTC). However, the role of circular RNA Pvt1 oncogene ( circPVT1) in PTC has rarely been reported. In this study, we aimed to investigate the function and mechanism of circPVT1 in PTC. The expression level of circPVT1, miR-195 and VEGFA were determined by reverse transcription‑quantitative PCR (RT‑qPCR). Fisher’s exact test was used to analyze the correlation between circPVT1 expression and PTC clinical features. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2ʹ-deoxyuridine (EdU) staining assay and transwell assay were conducted to evaluate the cell proliferation, migration and invasion ability. Dual-luciferase reporter and Western blot assay were conducted for evaluating the correlation between miR-195 and circPVT1 or VEGFA . The results of RT-PCR showed that the expression level of circPVT1 was significantly upregulated in PTC tissues and cell lines. After downregulating circPVT1 expression in PTC cells, the abilities of cell proliferation, migration, and invasion were obviously suppressed, and the Wnt/β-catenin signaling pathway was also repressed. Besides, miR-195 could both bind to PVT1 and VEGFA , while PVT1 could promote the expression of VEGFA by binding to miR-195 . Downregulation of VEGFA expression in PTC cells revealed weakened cell proliferation, migration, and invasion capacities, and restrained Wnt/β-catenin signaling pathway. Therefore, we demonstrated that circPVT1 could promote VEGFA expression by sponging miR-195. CircPVT1 could serve as a molecule sponge for miR-195 and mediate the ceRNA network to promote the expression of VEGFA , thus contributed to the malignant progression of PTC.

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Section: Discussionmentioning

confidence: 99%

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

Zeng¹,

Yuan²,

Zhou³

et al. 2021

Bioengineered

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“…Wnt exerts its effects through three signaling pathways, the most classic being the Wnt/β-catenin signaling pathway, mediated by β-catenin ( 42 ). It has been reported that the abnormal activation of the Wnt/β-catenin signaling pathway is involved in a number of diseases, including cancer, genetic diseases and organ fibrosis, as well as in the occurrence of EMT ( 43 ). Therefore, it was hypothesized that CtBP2, as a transcriptional co-repressor, may interact with TGIF and participate in the development of ESCC through the Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

CtBP2 interacts with TGIF to promote the progression of esophageal squamous cell cancer through the Wnt/β‑catenin pathway

Jiang

Huang

et al. 2021

Oncol Rep

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C-terminal-binding protein 2 (CtBP2), a transcriptional co-repressor, plays a main role in tumorigenesis and in the development of multiple tumors. Transforming growth interacting factor (TGIF) is involved in a number of cellular signal transduction pathways and is related to tumor occurrence and development. In the present study, the proteins interacting with CtBP2 were identified and the mechanisms underlying the biological activity of CtBP2 in esophageal squamous cell carcinoma (ESCC) were investigated. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to search for known proteins interacting with CtBP2, and co-immunoprecipitation (Co-IP) assay was performed to validate the interactions. Reverse transcription-quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and western blot analysis were performed to examine the expression levels of CtBP2 and TGIF in ESCC. The correlation between CtBP2 and TGIF was analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) by Pearson's correlation analysis, and the co-localization of CtBP2 with TGIF in the ECA109 cells was identified using immunofluorescence staining. XAV939 treatment, CCK-8, 5-ethynyl-2'-deoxyuridine (EdU) staining, wound healing and Transwell assays were performed to investigate the signaling pathways involved in the biological activity of CtBP2 in ECA109 cells. According to the results obtained from STRING and Co-IP analysis, an interaction between CtBP2 and TGIF was indicated, and these proteins were co-localized in the nucleus. CtBP2 and TGIF mRNA and protein expression levels were robustly and simultaneously increased in both ESCC tissues and cell lines. There was a direct correlation between CtBP2 and TGIF expression levels in ESCC tissues, and both were significantly associated with metastasis and survival. The TGIF and CtBP2 expression levels were significantly increased or decreased simultaneously, in ECA109 cells transfected with LV-CtBP2 or sh-CtBP2, and vice versa. According to the results of CCK-8 assay, EdU staining and Transwell assay, CtBP2 promoted the proliferation, migration and invasion of ECA109 cells through the Wnt/β-catenin pathway. On the whole, the present study demonstrates that CtBP2 interacts with TGIF and promotes the malignant progression of ESCC through the Wnt/β-catenin pathway.

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“…Canonical WNT signaling pathway mediated by WNT3A stabilizes β-catenin and leads to its association with the coactivator CBP for transcribing genes related to self-renewal, potency, and proliferation ( 77 ). However, the non-canonical WNT signaling pathway mediated by WNT5A induces the activation of various kinases such as PKC, CaMKII, SIK, AMPK, and MAPK ( 5 , 8 , 79 ). PKC further phosphorylates Ser89 of p300, which increases its affinity for β-catenin ( 77 ).…”

Section: Coactivators Regulating the Output Of The Wnt Signaling Path...mentioning

confidence: 99%

“…The PTB domain of IRS-1 then translocates the β-catenin-IRS-1 complex to the nucleus ( 143 ). β-catenin binding to IRS-1 with its C-terminus may thus prevent phosphorylation at its N-terminus by GSK3β, which primes β-catenin for ubiquitination and degradation ( 8 , 144 ). So, IRS-1, a docking protein for both IGF-1 and insulin receptors, can regulate the subcellular localization and activity of β-catenin in cells that are responsive to the mitogenic action of IGF-1 ( 142 , 145 ).…”

Section: Kinases Regulating the Activity Of β-Cateninmentioning

confidence: 99%

Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling

Shah

Kazi

2022

Front. Oncol.

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WNT/β-catenin signaling is a highly complex pathway that plays diverse roles in various cellular processes. While WNT ligands usually signal through their dedicated Frizzled receptors, the decision to signal in a β-catenin-dependent or -independent manner rests upon the type of co-receptors used. Canonical WNT signaling is β-catenin-dependent, whereas non-canonical WNT signaling is β-catenin-independent according to the classical definition. This still holds true, albeit with some added complexity, as both the pathways seem to cross-talk with intertwined networks that involve the use of different ligands, receptors, and co-receptors. β-catenin can be directly phosphorylated by various kinases governing its participation in either canonical or non-canonical pathways. Moreover, the co-activators that associate with β-catenin determine the output of the pathway in terms of induction of genes promoting proliferation or differentiation. In this review, we provide an overview of how protein phosphorylation controls WNT/β-catenin signaling, particularly in human cancer.

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Wnt/β-catenin signaling in cancers and targeted therapies

Cited by 285 publications

References 455 publications

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

CtBP2 interacts with TGIF to promote the progression of esophageal squamous cell cancer through the Wnt/β‑catenin pathway

Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling

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