Molecular Mechanism of Hippo–YAP1/TAZ Pathway in Heart Development, Disease, and Regeneration

Chen, Xiaoqing; Li, Yilang; Luo, Jia; Hou, Ning

doi:10.3389/fphys.2020.00389

Cited by 55 publications

(42 citation statements)

References 139 publications

(240 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The more recently discovered Hippo signalling pathway has been linked to cancer progression. This pathway is typically activated by changes in cell polarity, energy stress, transmembrane GPCRs and stiffness of the extracellular matrix [ 124 ]. The Hippo signalling pathway effector YAP has been shown to drive ZEB1 expression in breast cancer.…”

Section: Micro-environmental Cues Regulate the Reversible Balance mentioning

confidence: 99%

Intrinsic Balance between ZEB Family Members Is Important for Melanocyte Homeostasis and Melanoma Progression

Bruneel

Verstappe

Vandamme

et al. 2020

Cancers

View full text Add to dashboard Cite

It has become clear that cellular plasticity is a main driver of cancer therapy resistance. Consequently, there is a need to mechanistically identify the factors driving this process. The transcription factors of the zinc-finger E-box-binding homeobox family, consisting of ZEB1 and ZEB2, are notorious for their roles in epithelial-to-mesenchymal transition (EMT). However, in melanoma, an intrinsic balance between ZEB1 and ZEB2 seems to determine the cellular state by modulating the expression of the master regulator of melanocyte homeostasis, microphthalmia-associated transcription factor (MITF). ZEB2 drives MITF expression and is associated with a differentiated/proliferative melanoma cell state. On the other hand, ZEB1 is correlated with low MITF expression and a more invasive, stem cell-like and therapy-resistant cell state. This intrinsic balance between ZEB1 and ZEB2 could prove to be a promising therapeutic target for melanoma patients. In this review, we will summarise what is known on the functional mechanisms of these transcription factors. Moreover, we will look specifically at their roles during melanocyte-lineage development and homeostasis. Finally, we will overview the current literature on ZEB1 and ZEB2 in the melanoma context and link this to the ‘phenotype-switching’ model of melanoma cellular plasticity.

show abstract

Section: Micro-environmental Cues Regulate the Reversible Balance mentioning

confidence: 99%

Intrinsic Balance between ZEB Family Members Is Important for Melanocyte Homeostasis and Melanoma Progression

Bruneel

Verstappe

Vandamme

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…The combined results of high-throughput approaches, such as single-cell sequencing, ATAC-sequencing and ChIP-sequencing, and functional studies in animal models have revealed that the Hippo signaling pathway regulates epigenetics, transcriptomics, proteomics and cytologic changes to promote cardiomyocyte regeneration. Delicate manipulation of the Hippo-YAP signaling pathway has immense potential as a cell-free regenerative therapy for promoting adult heart renewal and treating heart disease [ 135 ]. Cardiomyocyte counts have been shown to increase by 40% after inducing YAP5SA overexpression and YAP5SA lineage cardiomyocytes coupled to pre-existing cardiomyocytes [ 101 ].…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

The Hippo Pathway in Cardiac Regeneration and Homeostasis: New Perspectives for Cell-Free Therapy in the Injured Heart

et al. 2020

View full text Add to dashboard Cite

Intractable cardiovascular diseases are leading causes of mortality around the world. Adult mammalian hearts have poor regenerative capacity and are not capable of self-repair after injury. Recent studies of cell-free therapeutics such as those designed to stimulate endogenous cardiac regeneration have uncovered new feasible therapeutic avenues for cardiac repair. The Hippo pathway, a fundamental pathway with pivotal roles in cell proliferation, survival and differentiation, has tremendous potential for therapeutic manipulation in cardiac regeneration. In this review, we summarize the most recent studies that have revealed the function of the Hippo pathway in heart regeneration and homeostasis. In particular, we discuss the molecular mechanisms of how the Hippo pathway maintains cardiac homeostasis by directing cardiomyocyte chromatin remodeling and regulating the cell-cell communication between cardiomyocytes and non-cardiomyocytes in the heart.

show abstract

“…Prenatal HFD exposure can impact DNA methylation of several genes related to dietary fat intake (62,63) as well as the levels and activity of several transcription factors that have been associated with brain development (64), such as transcriptional enhancer factor-1 (TEF-1), yes-associated protein-1 (YAP-1), and the family of peroxisome proliferatoractivated receptors (PPARs), that in turn effect the expression of some of the orexigenic neuropeptides (65)(66)(67)(68). The transcription factors TEF-1 and YAP-1 has been linked to prenatal HFD effects and plays a large role in organ formation and brain development during embryogenesis (69)(70)(71)(72), and activation of these transcription factors have been found to control neuronal proliferation and differentiation (73)(74)(75). Both TEF-1 and YAP-1 were inactivated or decreased during in utero HFD exposure and may promote increased neurogenesis events (65).…”

Section: Dietary Fat On Stimulating Neurochemical Systems In the Hypomentioning

confidence: 99%

Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus

Poon

2020

Front. Endocrinol.

View full text Add to dashboard Cite

Excessive dietary fat intake has extensive impacts on several physiological systems and can lead to metabolic and nonmetabolic disease. In animal models of ingestion, exposure to a high fat diet during pregnancy predisposes offspring to increase intake of dietary fat and causes increase in weight gain that can lead to obesity, and without intervention, these physiological and behavioral consequences can persist for several generations. The hypothalamus is a region of the brain that responds to physiological hunger and fullness and contains orexigenic neuropeptide systems that have long been associated with dietary fat intake. The past fifteen years of research show that prenatal exposure to a high fat diet increases neurogenesis of these neuropeptide systems in offspring brain and are correlated to behavioral changes that induce a pro-consummatory and obesogenic phenotype. Current research has uncovered several potential molecular mechanisms by which excessive dietary fat alters the hypothalamus and involve dietary fatty acids, the immune system, gut microbiota, and transcriptional and epigenetic changes. This review will examine the current knowledge of dietary fat-associated changes in the hypothalamus and the potential pathways involved in modifying the development of orexigenic peptide neurons that lead to changes in ingestive behavior, with a special emphasis on inflammation by chemokines.

show abstract

Molecular Mechanism of Hippo–YAP1/TAZ Pathway in Heart Development, Disease, and Regeneration

Cited by 55 publications

References 139 publications

Intrinsic Balance between ZEB Family Members Is Important for Melanocyte Homeostasis and Melanoma Progression

Intrinsic Balance between ZEB Family Members Is Important for Melanocyte Homeostasis and Melanoma Progression

The Hippo Pathway in Cardiac Regeneration and Homeostasis: New Perspectives for Cell-Free Therapy in the Injured Heart

Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus

Contact Info

Product

Resources

About