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

Abstract

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.

Metastatic Progression of Osteosarcomas: A Review of Current Knowledge of Environmental versus Oncogenic Drivers

“…This signaling pathway integrates mechanical and nutritional cues to drive the cell adaptation to ECM physical properties, cell junction modifications, oxygen level, or mechanical stresses ( Figure 2 ) [ 85 , 86 , 87 , 88 ]. The Hippo cascade is interconnected to multiple pathways, depending on the activation of receptor tyrosine kinases, transforming growth factor β, NOTCH, Wnt, G-protein-coupled receptors, or integrins, which together modulate YAP/TAZ nuclear translocation and transcriptional activities of transcriptional enhanced associate domain (TEAD) or Smad [ 89 , 90 , 91 ]. YAP/TAZ control the EMT process directly by modulating EMT genes or indirectly by modulating signaling pathways ( Figure 2 ) [ 92 ].…”

Lack of WWC2 Protein Leads to Aberrant Angiogenesis in Postnatal Mice

“…MST1/2-dependent phosphorylation leads to activation of LATS1/2, which culminates in phosphorylation YAP and TAZ preventing their import into the nucleus and terminating expression of YAP/TAZ-dependent target genes. Numerous proteins involved in regulation of cell growth, polarity, and homeostasis regulate activity of Hippo signalling pathways (for recent reviews see [ 4 , 5 ]).…”

YAP: The nexus between metabolism and cardiac remodeling

“…It was first implicated in cell proliferation and organ size regulation, but it also regulates metabolism (3,4). In cancer cells, YAP activity is essential for the induction of most of the genes involved in glycolytic pathways, which are thought to be necessary to meet the heightened demand for de novo synthesis of fatty acids, cholesterol, and amino acids (5).…”