Mechanisms of YAP/TAZ transcriptional control.

Giusy Battilana,Francesca Zanconato,Stefano Piccolo

doi:10.15698/cst2021.11.258

Abstract

Dysregulated gene expression is intrinsic to cell transformation, tumorigenesis and metastasis. Cancer-specific gene-expression profiles stem from gene regulatory networks fueled by genetic and epigenetic defects, and by abnormal signals of the tumor microenvironment. These oncogenic signals ultimately engage the transcriptional machinery on the cis -regulatory elements of a host of effector genes, through recruitment of transcription factors (TFs), co-activators and chromatin regulators. That said, whether gene-expression in cancer cells is the chaotic product of myriad regulations or rather a relatively ordered process orchestrated by few TFs (master regulators) has long remained enigmatic. Recent work on the YAP/TAZ co-activators has been instrumental to break new ground into this outstanding issue, revealing that tumor cells hijack growth programs that are active during development and regeneration through engagement of a small set of interconnected TFs and their nuclear partners.

Highlights

YAP/TAZ are essential mechanosensors of mammalian cells and are found disproportionally active in most human solid tumors
Whether gene expression in cancer cells is the chaotic product of myriad regulations or rather a relatively ordered process orchestrated by few transcription factors (TFs) has long remained enigmatic
What we do know is that YAP/TAZ activation in tumors is associated to several hallmarks of cancer, such as mutations in RTK/Ras signaling components, altered cell shape and biomechanical changes of the extracellular matrix (ECM; e.g., rigidity, fibrosity etc) [3, 4]

Summary

Introduction

YAP/TAZ are essential mechanosensors of mammalian cells and are found disproportionally active in most human solid tumors. YAP/TAZ and AP-1 proteins physically interact, either directly (PARK) or indirectly through TEADs [6], suggesting cooperative effects for robust activation of cis-regulatory elements and downstream transcriptional effects.

Results

Conclusion