A Potential Role of YAP/TAZ in the Interplay Between Metastasis and Metabolic Alterations

Yamaguchi, Hirohito; Taouk, Ghina M.

doi:10.3389/fonc.2020.00928

Cited by 74 publications

(68 citation statements)

References 192 publications

(253 reference statements)

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“…Most cells use membrane trafficking to continually rework their plasma membrane through ruffles, folds, endoand exocytosis, and it has been suggested that cells sense and regulate their volume and surface area through plasma membrane tension (73) . Recent evidence suggests that plasma membrane domains such clathrin coated pits and caveolae as well as lipid metabolism are regulated by and provide feedback to YAP/TAZ (74,75) . Thus, additional insight will be gained by experiments and models that explore the role of membrane trafficking, membrane surface roughness, and membrane lipid metabolism on regulating YAP/TAZ mechanotransduction.…”

Section: Discussionmentioning

confidence: 99%

Transfer function for YAP/TAZ nuclear translocation revealed through spatial systems modeling

Scott

Fraley

Rangamani

2020

Preprint

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YAP/TAZ is a master regulator of mechanotransduction whose functions rely on translocation from the cytoplasm to the nucleus in response to diverse physical cues. Substrate stiffness, substrate dimensionality, and cell shape are all input signals for YAP/TAZ, and through this pathway, regulate critical cellular functions and tissue homeostasis. Yet, the relative contributions of each biophysical signal and the mechanisms by which they synergistically regulate YAP/TAZ in realistic tissue microenvironments that provide multiplexed input signals remains unclear. For example, in simple 2D culture, YAP/TAZ nuclear localization correlates strongly with substrate stiffness, while in 3D environments, YAP/TAZ translocation can increase with stiffness, decrease with stiffness, or remain unchanged. Here, we develop a spatial model of YAP/TAZ translocation to enable quantitative analysis of the relationships between substrate stiffness, substrate dimensionality, and cell shape. Our model couples cytosolic stiffness to nuclear mechanics to replicate existing experimental trends, and extends beyond current data to predict that increasing substrate activation area through changes in culture dimensionality, while conserving cell volume, forces distinct shape changes that result in nonlinear effect on YAP/TAZ nuclear localization. Moreover, differences in substrate activation area versus total membrane area can account for counterintuitive trends in YAP/TAZ nuclear localization in 3D culture. Based on this multiscale investigation of the different system features of YAP/TAZ nuclear translocation, we predict that how a cell reads its environment is a complex information transfer function of multiple mechanical and biochemical factors. These predictions reveal design principles of cellular and tissue engineering for YAP/TAZ mechanotransduction.

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Section: Discussionmentioning

confidence: 99%

Transfer function for YAP/TAZ nuclear translocation revealed through spatial systems modeling

Scott

Fraley

Rangamani

2020

Preprint

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“…For instance, the clumping of actin stress fibers elicits nuclear translocation of the YAP/TAZ cytoplasmic complex. Once in the nucleus, these proteins act as transcriptional co-activators of genes involved in the regulation of cytoskeleton and FA constituents ( Figure 3 ) [ 116 ]. Accordingly, in what seems to be a clear feedforward positive loop, in various types of solid tumor, YAP causes matrix stiffness and fiber densification by increasing stromal deposition of collagen [ 117 ].…”

Section: Three-dimensional (3d) Ecm-mimicking Scaffolds: Sensing mentioning

confidence: 99%

Modeling the Mechanobiology of Cancer Cell Migration Using 3D Biomimetic Hydrogels

Morales

Cortés-Domínguez

Ortiz‐de‐Solórzano

2021

Gels

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Understanding how cancer cells migrate, and how this migration is affected by the mechanical and chemical composition of the extracellular matrix (ECM) is critical to investigate and possibly interfere with the metastatic process, which is responsible for most cancer-related deaths. In this article we review the state of the art about the use of hydrogel-based three-dimensional (3D) scaffolds as artificial platforms to model the mechanobiology of cancer cell migration. We start by briefly reviewing the concept and composition of the extracellular matrix (ECM) and the materials commonly used to recreate the cancerous ECM. Then we summarize the most relevant knowledge about the mechanobiology of cancer cell migration that has been obtained using 3D hydrogel scaffolds, and relate those discoveries to what has been observed in the clinical management of solid tumors. Finally, we review some recent methodological developments, specifically the use of novel bioprinting techniques and microfluidics to create realistic hydrogel-based models of the cancer ECM, and some of their applications in the context of the study of cancer cell migration.

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“…Among the thousands of genes whose expression is modified upon reprogramming, many are directly or indirectly related to metabolism [ 5 , 6 , 115 ]. Our understanding of the role exerted by YAP/TAZ in regulating metabolism is rapidly expanding [ 116 ]. It is worth noting that not only may their activity be influenced by the cellular metabolic status, but they are also able to promote a metabolic remodeling process, which may accompany cellular adaptation to changes in the environmental conditions ( Figure 2 ).…”

Section: Yap and Taz Are Modulators Of Metabolic Reprogrammingmentioning

confidence: 99%

“…YAP and TAZ are now recognized to reprogram cellular metabolic pathways, allowing cells to adapt to mutable environmental conditions [ 116 , 126 ]. They integrate physiological and environmental signals by modulating transcriptional programs to regulate the expression of metabolic enzymes and nutrient transporters.…”

Section: Yap and Taz Are Modulators Of Metabolic Reprogrammingmentioning

confidence: 99%

YAP and TAZ Mediators at the Crossroad between Metabolic and Cellular Reprogramming

et al. 2021

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Cell reprogramming can either refer to a direct conversion of a specialized cell into another or to a reversal of a somatic cell into an induced pluripotent stem cell. It implies a peculiar modification of the epigenetic asset and gene regulatory networks needed for a new cell, to better fit the new phenotype of the incoming cell type. Cellular reprogramming also implies a metabolic rearrangement, similar to that observed upon tumorigenesis, with a transition from oxidative phosphorylation to aerobic glycolysis. The induction of a reprogramming process requires a nexus of signaling pathways, mixing a range of local and systemic information, and accumulating evidence points to the crucial role exerted by the Hippo pathway components Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ). In this review, we will first provide a synopsis of the Hippo pathway and its function during reprogramming and tissue regeneration, then we introduce the latest knowledge on the interplay between YAP/TAZ and metabolism and, finally, we discuss the possible role of YAP/TAZ in the orchestration of the metabolic switch upon cellular reprogramming.

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A Potential Role of YAP/TAZ in the Interplay Between Metastasis and Metabolic Alterations

Cited by 74 publications

References 192 publications

Transfer function for YAP/TAZ nuclear translocation revealed through spatial systems modeling

Transfer function for YAP/TAZ nuclear translocation revealed through spatial systems modeling

Modeling the Mechanobiology of Cancer Cell Migration Using 3D Biomimetic Hydrogels

YAP and TAZ Mediators at the Crossroad between Metabolic and Cellular Reprogramming

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