De-regulation of YAP1 activity plays important roles in the progression and therapy resistance of several human cancers.
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YAP1 activity can be de-regulated by inactivation of Hippo regulators, by intersecting pathways, miRNAs, or viral oncogenes.
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YAP1 fusions are the likely oncogenic drivers in several human cancers and constitute a type of activating YAP1 mutation.
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Efficacy of anti-YAP1 therapy might depend on whether YAP1 is required for the maintenance in a particular tumor type.
Abstract
YAP1 is a transcriptional co-activator whose activity is controlled by the Hippo signaling pathway. In addition to important functions in normal tissue homeostasis and regeneration, YAP1 has also prominent functions in cancer initiation, aggressiveness, metastasis, and therapy resistance. In this review we are discussing the molecular functions of YAP1 and its roles in cancer, with a focus on the different mechanisms of de-regulation of YAP1 activity in human cancers, including inactivation of upstream Hippo pathway tumor suppressors, regulation by intersecting pathways, miRNAs, and viral oncogenes. We are also discussing new findings on the function and biology of the recently identified family of YAP1 gene fusions, that constitute a new type of activating mutation of YAP1 and that are the likely oncogenic drivers in several subtypes of human cancers. Lastly, we also discuss different strategies of therapeutic inhibition of YAP1 functions.
