WNT signaling in stem cell differentiation and tumor formation

Ouyang, Hong; Zhuo, Yehong; Zhang, Kang

doi:10.1172/jci69324

Cited by 14 publications

(5 citation statements)

References 13 publications

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“…Wnt can secrete glycoprotein through binding with receptors on the cell membranes ( 77 ) and can activate intracellular signaling pathways, which regulate the expression of target genes. Thus, cell proliferation, differentiation and apoptosis can be regulated, and various diseases will be caused, even tumorigenesis ( 75 , 78 , 79 ). Wnt pathways contain the canonical (Wnt/β-catenin), non-canonical (Wnt/JNK pathway) and Ca 2+ pathways ( 80 , 81 ).…”

Section: Regulation Of the Wnt/β-catenin Signaling Pathway In Glaumentioning

confidence: 99%

Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review)

et al. 2017

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Glaucoma is the leading cause of irreversible blindness worldwide and there is no effective treatment thus far. The trabecular meshwork has been identified as the major pathological area involved. Certain signaling pathways in the trabecular meshwork, including the Wnt, lysophosphatidic acid and transforming growth factor-β pathways, have been identified as novel therapeutic targets in glaucoma treatment. Meanwhile, it has been reported that key proteins in these pathways, particularly the primary transcription regulator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), exhibit interactions with the Hippo pathway. The Hippo pathway, which was first identified in Drosophila, has drawn great focus with regard to various aspects of studies in recent years. One role of the Hippo pathway in the regulation of organ size was indicated by more recent evidence. Defining the relevant physiological function of the Hippo pathway has proven to be extremely complicated. Studies have ascribed a role for the Hippo pathway in an overwhelming number of processes, including cell proliferation, cell death and cell differentiation. Therefore, the present review aimed to unravel the roles of YAP and TAZ in the Hippo pathway and the pathogenesis of glaucoma. Furthermore, a new and creative study for the treatment of glaucoma is provided.

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Section: Regulation Of the Wnt/β-catenin Signaling Pathway In Glaumentioning

confidence: 99%

Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review)

et al. 2017

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“…Undoubtedly, Wnt signaling has many more cellular functionsfor example, control of cell differentiation, cell migration, cancer metastasis and even energy homeostasis (Rao and Kühl, 2010;Elghazi et al, 2012;Ouyang et al, 2013). How these activities are coordinated with cell cycle progression is largely unknown.…”

Section: S-g2-specific Functions Of the Wnt-b-catenin Signalingmentioning

confidence: 99%

The S-G2 phase enriched β-catenin/TCF complex ensures cell survival and cell cycle progression

Ding

Tang

et al. 2014

Journal of Cell Science

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BSTRACTWnt-b-catenin (b-catenin is also known as CTNNB1 in human) signaling through the b-catenin-TCF complex plays crucial roles in tissue homeostasis. Wnt-stimulated b-catenin-TCF complex accumulation in the nucleus regulates cell survival, proliferation and differentiation through the transcription of target genes. Compared with their levels in G1, activation of the receptor LRP6 and cytosolic b-catenin are both upregulated in G2 cells. However, accumulation of the Wnt pathway negative regulator AXIN2 also occurs in this phase. Therefore, it is unclear whether Wnt signaling is active in G2 phase cells. Here, we established a bimolecular fluorescence complementation (BiFC) biosensor system for the direct visualization of the b-catenin-TCF interaction in living cells. Using the BiFC biosensor and co-immunoprecipitation experiments, we demonstrate that levels of the nucleus-localized b-catenin-TCF complex increase during the S and G2 phases, and declines in the next G1 phase. Accordingly, a subset of Wnt target genes is transcribed by the b-catenin-TCF complex during both the S and G2 phases. By contrast, transient inhibition of this complex disturbs both cell survival and G2/M progression. Our results suggest that in S and G2 phase cells, Wnt-b-catenin signaling is highly active and functions to ensure cell survival and cell cycle progression.

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“…Wnts are secreted glycoproteins that act as growth factors and regulate various cellular functions including proliferation, differentiation, death, migration and polarity, through the activation of multiple intracellular signaling cascades by binding to various receptors including Frizzleds. There are 19 human Wnt proteins and 10 Frizzled (Fzd) receptors, all exhibiting unique expression patterns and serving distinct roles in normal development and throughout life .…”

Section: Introductionmentioning

confidence: 99%

Discovery and Optimization of a Porcupine Inhibitor

et al. 2015

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Wnt proteins regulate various cellular functions and serve distinct roles in normal development throughout life. Wnt signaling is dysregulated in various diseases including cancers. Porcupine (PORCN) is a membrane-bound O-acyltransferase that palmitoleates the Wnts and hence is essential for their secretion and function. The inhibition of PORCN could serve as a therapeutic approach for the treatment of a number of Wnt-dependent cancers. Herein, we describe the identification of a Wnt secretion inhibitor from cellular high throughput screening. Classical SAR based cellular optimization provided us with a PORCN inhibitor with nanomolar activity and excellent bioavailability that demonstrated efficacy in a Wnt-driven murine tumor model. Finally, we also discovered that enantiomeric PORCN inhibitors show very different activity in our reporter assay, suggesting that such compounds may be useful for mode of action studies on the PORCN O-acyltransferase.

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WNT signaling in stem cell differentiation and tumor formation

Cited by 14 publications

References 13 publications

Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review)

Mutual regulation of the Hippo/Wnt/LPA/TGF‑β signaling pathways and their roles in glaucoma (Review)

The S-G2 phase enriched β-catenin/TCF complex ensures cell survival and cell cycle progression

Discovery and Optimization of a Porcupine Inhibitor

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