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Neuroendocrine Interactions in the Control of Glucose- and Energy Homeostasis
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
The WNT pathway was first described in 1976 when it was reported that Drosophila Melanogaster has a wingless phenotype when this pathway is mutated (92). In 1982, the same signalling cascade was found to promote tumour formation in mice, and therefore given the term ‘integration-1 (int1)’ (93). ‘Wingless’ and ‘int1’ were later combined, and thus, the WNT pathway was coined. The WNT signalling pathway is evolutionarily highly conserved and is classically known for its role in embryogenesis and tumorigenesis (94). Its ligands (WNTs) are involved in three different pathways: the WNT/β-catenin pathway (also known as the canonical WNT pathway), the planar cell polarity pathway, and the WNT/Ca2+ pathway. The canonical WNT pathway is activated when a WNT ligand binds to the frizzled (Fzd) receptor, which subsequently forms a complex with the co-receptor lipoprotein related protein (LRP) 5/6. This causes dishevelled (Dvl) to phosphorylate LRP, which then inactivates GSK3β. Next, GSK3β inactivation decreases phosphorylation of the transcriptional co-activator β-catenin. Stabilized β-catenin then enters the nucleus where it associates with transcription factors of the lymphoid enhancer factor (LEF)/T cell factor (TCF) family, to ultimately regulate the transcription of downstream target genes such as cyclin D1 and axin 2 (95).
Microneedling
Published in Rubina Alves, Ramon Grimalt, Techniques in the Evaluation and Management of Hair Diseases, 2021
Rachita S. Dhurat, Sanober Burzin Daruwalla
Wnt signals play a key role in hair follicle morphogenesis, hair shaft differentiation and follicular cycling [18]. Activation of Wnt/β-catenin signaling is important not only for initiation and maintenance of hair morphogenesis but also for HF regeneration and growth of the hair shaft [19, 20]. Wnt3a and Wnt10b both mediate the canonical Wnt signaling pathway, which induces β-catenin stabilization [21]. In particular, Wnt10b prominently promoted proliferation and maintained trichogenesis-promoting ability [17].
Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
Wnt has become a substantial new target for drug development to treat cancer because of its signaling cascade that plays a central role in regulating significant functions of malignant epithelial cells. Wnt ligands and signals drive the Wnt signaling pathway through canonical (β-catenin dependent) or non-canonical (β-catenin independent) paths. The Wnt ligand binds to various transmembrane receptors, such as Frizzled (FZD), Receptor tyrosine kinases (RTKs) and Receptor tyrosine kinase-like orphan receptor (ROR) 1 or ROR2. The pathway is activated with the binding of Wnt ligand to its receptor, followed by the activation of β-catenin. In the absence of Wnt ligand, β-catenin undergoes phosphorylation by a destruction complex containing glycogen synthase kinase 3b (GSK3b), adenomatous polyposis coli (APC) and axin, followed by degradation of β-catenin.
miR-637 Inhibits Osteogenic Differentiation of Human Intervertebral Disc Cartilage Endplate Stem Cells by Targeting WNT5A
Published in Journal of Investigative Surgery, 2022
Yunsheng Chen, Qin Chen, Mingliang Zhong, Canhua Xu, Yaohong Wu, Rongchun Chen
The Wnt signaling pathway is an important pathway for vertebrate embryogenesis, differentiation, cell movement, and adult tissue homeostasis [14]. The mechanism of the Wnt signaling pathway in stem cell osteogenic differentiation has been extensively studied [15–17]. As a key protein in the Wnt pathway “Wnt/Ca2+ pathway” branch, WNT5A is reported to be involved in the regulation of osteogenic differentiation and chondrogenesis [18–20]. For instance, miR-148a from adipose-derived MVs promotes adipogenic differentiation of BMSCs and inhibits osteogenic differentiation by suppressing the Wnt5a/Ror2 pathway [21]. Wnt5a/FZD4 mediated osteogenic differentiation of BMSCs provoked by mechanical stretching [18]. miR-1297 inhibits osteogenesis of BMSC by targeting WNT5A and promotes the progression of osteoporosis [20]. Exosomes derived from HMSCs with overexpressed miR-92A-3p enhance chondrogenesis by targeting WNT5A [19]. However, no domestic or foreign literature has reported that miR-637 inhibits osteogenic differentiation of human CESCs by targeting WNT5A. The present study was intended to probe into the mechanism of miR-637 in osteogenic differentiation of human CESC by targeting WNT5A.
Non-Digestible Carbohydrate and the Risk of Colorectal Neoplasia: A Systematic Review
Published in Nutrition and Cancer, 2021
Mingyue Rao, Chenlin Gao, Jing Hou, Junling Gu, Betty Yuen Kwan Law, Yong Xu
However, RS/inulin has been shown to have positive results in some animal models and In Vitro experiments (41,42), so it is necessary to review the mechanism involved in cancer prevention. The WNT signaling pathway is associated with proliferation, migration, and differentiation and is known to influence carcinogenesis (43). High dose RS reduces WNT pathway activity in carcinogen-treated rats (44). Butyrate, one of the products of RS, increases the level of unphosphorylated β-catenin in the WNT pathway of eight CRC cell lines (45), and β-catenin activates downstream proliferative signaling after being phosphorylated. Global demethylation of DNA is observed in many cancers (46). Shin et al. reported that butyrate restores SFRP1 expression following promoter demethylation to inhibit the WNT pathway (47). Butyrate has been studied as a histone deacetylase inhibitor, and it may restore expression of silenced acetylation genes leading to restoration of normal levels of proliferation, differentiation, and apoptosis (48). An alternative explanation would be aberrant expression of miRNAs, resulting in altered expression (usually downregulation) of target genes involved in the regulation of proliferation, migration, and differentiation, which may contribute to carcinogenesis (49). A microarray analysis and subsequent validation confirmed that expression of the miR17-92 and miR-106a-363 clusters in HT29 cells treated with butyrate decreases significantly (35). This is the mechanism that has been validated by Worthley et al. and may support RS efficacy in cancer prevention (22).
Raphanus sativus L. seed extracts induce apoptosis and reduce migration of oral squamous cell carcinoma KB and KBCD133+cells by downregulation of β-catenin
Published in Nutrition and Cancer, 2020
Kyuhyeon Ahn, Hyeongjoon Ji, Hye-Eun Kim, Hyejoung Cho, Qiaochu Sun, Shuhan Shi, Yuzhu He, Byung-Gook Kim, Okjoon Kim
β-catenin is an important mediator of the Wnt signaling pathway. So, we analyzed the Wnt/β-catenin signaling pathway to understand the molecular mechanisms responsible for the effects of RSLS. In KB and KBCD133+ cells, the expression levels of β-catenin and its target protein TCF-4 decreased in a dose-dependent manner (Fig. 4D). In parallel with the decrease in β-catenin levels, a marked increase in the expression of axin and a corresponding decrease in phosphorylation of GSK-3β were observed, whether the expression of CD133, HDAC6, and DVL remained unchanged following treatment with the RSLS extracts (Fig. 5A). While the DVL level remained unchanged, axin levels increased dose-dependently in both KB and KBCD133+ cells (Fig. 5D). No other significant difference was observed in the overall GSK-3β expression between KB and KBCD133+ cells treated with various concentrations of the RSLS extracts (Fig. 5A). However, the p-GSK-3β level and p-GSK-3β/t-GSK-3β ratio were significantly decreased in RSLS-treated cells in a dose-dependent manner, especially after normalization to the GSK-3β total protein levels (Fig. 5E). The levels of β-catenin, a downstream target of GSK-3β, were also significantly and dose-dependently decreased in the RSLS extracts-treated cells (Fig. 5B).