TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression

Hwang, Jae Ho; Kim, A. Rum; Kim, Kyung Min; Park, Jung Il; Oh, Ho Taek; Moon, Sung Ah; Byun, Mi Ran; Jeong, Hana; Kim, Hyo Kyung; Yaffe, Michael B.; Hwang, Eun Sook; Hong, Jeong Ho

doi:10.1038/s41467-019-08287-x

Cited by 43 publications

(44 citation statements)

References 55 publications

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“…The two arms downstream of insulin/IGF, PI3K and MAPK signalling pathways are altered in T2D and CRC. Crosstalk between PI3K and Wnt signalling through GSK3B inactivation or between Wnt and Hippo through YAP/TAZ and their regulation by metabolites illustrates the importance of their correct wiring for signalling in T2D and CRC (Santinon et al 2016, Hwang et al 2019. Furthermore, leptin/adiponectin imbalances enhance JAK/STAT signalling as inflammatory cytokines do, reinforcing the link with CRC.…”

Section: Remodelling Crc Cell Signalling By Hormonal Alterations In T2dmentioning

confidence: 99%

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Gutiérrez-Salmerón

Lucena

Chocarro-Calvo

et al. 2021

Endocrine-Related Cancer

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The existence of molecular links that facilitate colorectal cancer (CRC) development in the population with type 2 diabetes (T2D) is supported by substantial epidemiological evidence. This review summarizes how the systemic metabolic and hormonal imbalances from T2D alter CRC cell metabolism, signaling and gene expression as well as their reciprocal meshing, with an overview of CRC molecular subtypes and animal models to study the diabetes-CRC cancer links. Metabolic and growth factor checkpoints ensure a physiological cell proliferation rate compatible with limited nutrient supply. Hyperinsulinemia and hyperleptinemia in prediabetes and excess circulating glucose and lipids in T2D, overcome formidable barriers for tumor development. Increased nutrient availability favours metabolic reprogramming, alters signaling and generate mutations and epigenetic modifications, through increased reactive oxygen species and oncometabolites. The reciprocal control between metabolism and hormone signaling is lost in diabetes. Excess adipose tissue at the origin of T2D, unbalances adipokine (leptin / adiponectin) secretion ratios and function and disrupts the Insulin/IGF axes. Leptin/adiponectin imbalances in T2D are believed to promote proliferation and invasion of CRC cancer cells and contribute to inflammation, an important component of CRC tumorigenesis. Disruption of the Insulin/IGF axes in T2D targets systemic and CRC cell metabolic reprogramming, survival and proliferation. Future research to clarify the molecular diabetes-CRC links will help to prevent CRC and reduce its incidence in the diabetic population and must guide therapeutic decisions.

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Section: Remodelling Crc Cell Signalling By Hormonal Alterations In T2dmentioning

confidence: 99%

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Gutiérrez-Salmerón

Lucena

Chocarro-Calvo

et al. 2021

Endocrine-Related Cancer

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“…Understanding how beige selective pathways are induced can provide new insights that could allow for the targeted selection of this metabolically favorable phenotype of adipocyte. Although developmentally of different origin (muscle-like), YAP/TAZ signalling has also been shown to regulate insulin signalling in muscle where TAZ has shown to stimulate insulin sensitivity by upregulating IRS1 which mediates GLUT4 uptake of glucose in muscle cells [97]. Brown adipocytes (BAT) are functionally similar to beige adipocytes.…”

Section: Obesitymentioning

confidence: 99%

Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Cobbaut

Karagil

Bruno

et al. 2020

Cells

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In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions.

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“…Previous studies revealed that Wnt/β-catenin signaling regulates IRS-1 through β-catenin/TCF4 binding to the regulatory sequence of the murine IRS-1 promoter in mouse skeletal muscle C2C12 cells and rat H4IIE hepatoma cells (Hwang et al, 2019;Yoon et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Activation of Wnt/β‐catenin signaling restores insulin sensitivity in insulin resistant neurons through transcriptional regulation of IRS‐1

Tian

Tan

Jia

et al. 2020

Journal of Neurochemistry

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Aberrant expression and phosphorylation of insulin receptor substrate 1 (IRS-1) contribute to brain insulin resistance. However, the underlying mechanism remains elusive. The insulin signaling and Wnt/β-catenin signaling are two critical pathways for normal cellular function, which interact in both peripheral tissues and the brain and may contribute to insulin resistance. In this study, we aimed to investigate the regulation of IRS-1 and its downstream insulin signaling by Wnt/β-catenin signaling in primary neurons. We found that the Wnt agonist Wnt3a enhances the insulin signaling in neurons at the basal state via up-regulation of IRS-1. Moreover, Wnt3a up-regulates IRS-1 expression and effectively ameliorates insulin resistance in rat primary neurons induced by chronic high insulin exposure. The insulin-mediated glucose uptake is also stimulated by Wnt3a at both basal and insulin resistant states. We observed that Wnt activation up-regulates IRS-1 gene transcription and the subsequent protein expression in SH-SY5Y cells and rat primary neurons via different means of Wnt/βcatenin signaling activation, including S33Y β-catenin over-expression, CHIR99021 and Wnt3a treatment. We further clarified the molecular mechanism of IRS-1 transcriptional activation by Wnt/β-catenin signaling. The Wnt transcription factor TCF4 binds to the −529 bp to −516 bp of the human IRS-1 promoter fragment and activates IRS-1 transcription. Overall, these data suggested that Wnt/β-catenin signaling positively regulates IRS-1 and insulin signaling and protects against insulin resistance in neurons.

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TAZ couples Hippo/Wnt signalling and insulin sensitivity through Irs1 expression

Cited by 43 publications

References 55 publications

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Metabolic and hormonal remodeling of colorectal cancer cell signaling by diabetes

Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Activation of Wnt/β‐catenin signaling restores insulin sensitivity in insulin resistant neurons through transcriptional regulation of IRS‐1

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