The Wnt/β-catenin Signaling Pathway in Epithelial Mesenchymal Transition

Journal, PostDoc; Menezes, Mitchell E.

doi:10.14304/surya.jpr.v2n7.1

Cited by 4 publications

(4 citation statements)

References 67 publications

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“…Canonical Wnt signaling is initiated by a WNT ligand, which is usually WNT7A or WNT3, and leads to the stabilization of CTNNB (b-catenin). Like Notch signaling, canonical Wnt signaling also causes GSK3b phosphorylation, allowing the accumulation and nuclear localization of SNAI1 and SNAI2 (Wu et al, 2012;Menezes, 2014). Further, the complex formed by CTNNB and TCF activates the transcription of many of the genes regulated by canonical Wnt signaling (Menezes, 2014), including SNAI2 (Conacci-Sorrell et al, 2003), TWIST1 (Howe et al, 2003), and ZEB1 (Sánchez-Tilló et al, 2011;Sanchez-Tillo et al, 2014).…”

Section: The Molecular Signaling Pathways Involved In Endmt Regulationmentioning

confidence: 99%

A Computational Model of the Endothelial to Mesenchymal Transition

2020

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Endothelial cells (ECs) form the lining of lymph and blood vessels. Changes in tissue requirements or wounds may cause ECs to behave as tip or stalk cells. Alternatively, they may differentiate into mesenchymal cells (MCs). These processes are known as EC activation and endothelial-to-mesenchymal transition (EndMT), respectively. EndMT, Tip, and Stalk EC behaviors all require SNAI1, SNAI2, and Matrix metallopeptidase (MMP) function. However, only EndMT inhibits the expression of VE-cadherin, PECAM1, and VEGFR2, and also leads to EC detachment. Physiologically, EndMT is involved in heart valve development, while a defective EndMT regulation is involved in the physiopathology of cardiovascular malformations, congenital heart disease, systemic and organ fibrosis, pulmonary arterial hypertension, and atherosclerosis. Therefore, the control of EndMT has many promising potential applications in regenerative medicine. Despite the fact that many molecular components involved in EC activation and EndMT have been characterized, the system-level molecular mechanisms involved in this process have not been elucidated. Toward this end, hereby we present Boolean network model of the molecular involved in the regulation of EC activation and EndMT. The simulated dynamic behavior of our model reaches fixed and cyclic patterns of activation that correspond to the expected EC and MC cell types and behaviors, recovering most of the specific effects of simple gain and loss-of-function mutations as well as the conditions associated with the progression of several diseases. Therefore, our model constitutes a theoretical framework that can be used to generate hypotheses and guide experimental inquiry to comprehend the regulatory mechanisms behind EndMT. Our main findings include that both the extracellular microevironment and the pattern of molecular activity within the cell regulate EndMT. EndMT requires a lack of VEGFA and sufficient oxygen in the extracellular microenvironment as well as no FLI1 and GATA2 activity within the cell. Additionally Tip cells cannot undergo EndMT directly. Furthermore, the specific conditions that are sufficient to trigger EndMT depend on the specific pattern of molecular activation within the cell.

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Section: The Molecular Signaling Pathways Involved In Endmt Regulationmentioning

confidence: 99%

A Computational Model of the Endothelial to Mesenchymal Transition

2020

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“…The regulatory effects of DAC and curcumin on cell migration were also investigated, and the results showed that either single or combination treatment with DAC and curcumin inhibited SKOV3 cell migration. One crucial EMT-associated gene, vimentin, is also a target gene of the Wnt/β-catenin signaling pathway 54 . Our results showed that not only vimentin, but also fibronectin, were down-regulated, whereas E-cadherin was up-regulated, by combined treatment with 5 μM DAC and 20 μM curcumin.…”

Section: Discussionmentioning

confidence: 99%

Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line

Yen

Tsao

Lin

et al. 2019

Sci Rep

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The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The curcumin-rich Curcuma longa has been reported to potent anti-cancer property involved in epigenetic regulation to inhibit tumor suppressor gene methylation and re-expression. In a compounds screening, we found that curcumin can inhibit Wnt/β-catenin signaling. Therefore, the aim of this study was to investigate the effects of curcumin on SFRP5 DNA methylation modification in an ovarian cancer cell line (SKOV3). SKOV3 cells were treated with DMSO, 10 μM 5-aza-2′-deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin, and 20 μM curcumin combined with 5 μM DAC for 96 hours, following which RNA and proteins were extracted for further analysis. The results showed that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation, migration through EMT (epithelial–mesenchymal transition) process regulation, total DNMT activity, especially in DNMT3a protein expression, and may also regulate tumor suppressor gene SFRP5 expression involved in the Wnt/β-catenin signaling pathway. The combined treatment attenuated ovarian cancer development.

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“…Wnt/β-catenin signaling is a classic pathway involved in modulating the development of cancer cells, i.e., proliferation, resistance, differentiation, motility, adhesion, and apoptosis of cancer cells [13]. However, several signal transducers that affect β-catenin activity (phosphorylation/degradation) are Glycogen Synthase Kinase 3β (GSK-3β), Axin, and adenomatous polyposis coli [9], [14].…”

Section: Introductionmentioning

confidence: 99%

Wnt Signaling and Cadherin Expressions in Different Staging of Colorectal Cancer as Biomarkers for Metastasis: Study of SW480, COLO 320DM, and HCT116 Cellines

Luminturahardjo

Rahajoe

Soeatmadji

et al. 2021

Open Access Maced J Med Sci

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BACKGROUND: Early metastases is still unresolved problem in cancer management, eventually in colorectal cancer (CRC). In addition, many markers are useful just only in the late stage of CRC. AIM: This study evaluates the differences in the expression intensity of nuclear β-catenin, cytoplasmic β-catenin, E-cadherin, and N-cadherin between CRC SW480 cell line as control group and COLO320DM and HCT116 cell lines as case groups. MATERIALS AND METHODS: This study applied experimental research design with the different test methods. Culture growing and subcultures manufacturing for the CRC cell line models were done initially and followed by the immunofluorescence method by administering antibodies on β-catenin, E-cadherin, and N-cadherin, and continued with staining process using fluorescein-5-isothiocyanate and 4’, 6-diamidino-2-phenylindole. Observations were done using an immunofluorescence microscope. Calculation of area density in each cell to perceive the expressions of cytoplasmic and nuclear β-catenin, E-cadherin, and N-cadherin was conducted using ImageJ software, resulted in mean fluorescence intensity. RESULTS: There are significant differences in the expressions of cytoplasmic β-catenin, nuclear β-catenin, E-cadherin, and N-cadherin among SW480, COLO320DM, and HCT116 cell lines (p < 0.05). Despite no significant differences in cytoplasmic and nuclear β-catenin expressions between SW480 and HCT116 cell lines, and in E-cadherin and N-cadherin expressions between COLO320DM and HCT116 cell lines (p > 0.05). SW480 cell line has a higher expression of nuclear β-catenin than the cytoplasm (p < 0.05). CONCLUSION: This study reveals differences in the expression of nucleic and cytoplasmic β-catenin, E-cadherin, and N-cadherin in three stages of CRC (Duke B, C, and D) refer to different activation invasion, migration, and metastatic processes. Furthermore, the high expression of nuclear β-catenin and N-cadherin in the early stage of CRC indicate there is a metastatic process in that stage, so nuclear β-catenin and cadherin can be considered as potential biomarkers in the early stage of this cancer.

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The Wnt/β-catenin Signaling Pathway in Epithelial Mesenchymal Transition

Cited by 4 publications

References 67 publications

A Computational Model of the Endothelial to Mesenchymal Transition

A Computational Model of the Endothelial to Mesenchymal Transition

Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line

Wnt Signaling and Cadherin Expressions in Different Staging of Colorectal Cancer as Biomarkers for Metastasis: Study of SW480, COLO 320DM, and HCT116 Cellines

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