Volume 9, Issue 3 e371
Advanced Review

Hippo-Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Benjamin J. van Soldt

Benjamin J. van Soldt

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care Medicine, Columbia University Irving Medical Center, New York, New York

Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York

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Wellington V. Cardoso

Corresponding Author

Wellington V. Cardoso

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care Medicine, Columbia University Irving Medical Center, New York, New York

Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York

Correspondence

Wellington V. Cardoso, Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care Medicine, Columbia University Irving Medical Center, New York, NY.

Email: [email protected]

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First published: 11 December 2019
Citations: 21

Funding information: National Heart, Lung, and Blood Institute, Grant/Award Number: NIH-NHLBI R35- HL135834-01

Abstract

The Hippo pathway has emerged as a crucial integrator of signals in biological events from development to adulthood and in diseases. Although extensively studied in Drosophila and in cell cultures, major gaps of knowledge still remain on how this pathway functions in mammalian systems. The pathway consists of a growing number of components, including core kinases and adaptor proteins, which control the subcellular localization of the transcriptional co-activators Yap and Taz through phosphorylation of serines at key sites. When localized to the nucleus, Yap/Taz interact with TEAD transcription factors to induce transcriptional programs of proliferation, stemness, and growth. In the cytoplasm, Yap/Taz interact with multiple pathways to regulate a variety of cellular functions or are targeted for degradation. The Hippo pathway receives cues from diverse intracellular and extracellular inputs, including growth factor and integrin signaling, polarity complexes, and cell–cell junctions. This review highlights the mechanisms of regulation of Yap/Taz nucleocytoplasmic shuttling and their implications for epithelial cell behavior using the lung as an intriguing example of this paradigm.

This article is categorized under:

  • Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms
  • Signaling Pathways > Cell Fate Signaling
  • Establishment of Spatial and Temporal Patterns > Cytoplasmic Localization

Graphical Abstract

Hippo-Yap/Taz integrate signals from multiple sources to modulate cell behavior. Cell–cell junctions, apical-basal polarity, and nutrient sensing pathways induce Yap/Taz cytoplasmic sequestration for cell quiescence or differentiation. Growth factor signaling, integrin signaling, and metabolic pathways induce nuclear Yap/Taz and transcriptional activity to foster cell proliferation and stemness.

CONFLICT OF INTEREST

The authors have declared no conflicts of interest for this article.