About this Research Topic
The evolutionarily conserved Hippo signaling pathway plays crucial roles in organ size control, tissue homeostasis and immune response. Dysregulations of this pathway have been closely associated with diverse human diseases including developmental defects and various cancers. The Hippo pathway mainly consists of a cascade of kinase-mediated phosphorylation events that intricately control cytoplasmic/nuclear localization of the key downstream effectors YAP or TAZ. Inactivation of Hippo results in nuclear translocation of YAP/TAZ and subsequent binding with TEAD family of transcription factors, which then stimulate expression of a wide spectrum of genes involved in cell proliferation, metabolism, tissue repair and regeneration. Thus, understanding the regulatory mechanisms of Hippo pathway is essential for elucidating the nature of tissue homeostasis and organ size control, as well as for developing advanced strategies of targeted cancer therapy and precise medicine.
Despite great progresses achieved over the last decade, the precise physiological and pathological roles of Hippo pathway are still mysterious. It is speculated that Hippo signaling controls organ size via crosstalk with multiple other cellular pathways and processes. However, the mechanisms of initiating and/or sensing extracellular signals in a context of cell-cell communications are still elusive; how these signals are transduced and then integrated with metabolic and epigenetic cues to ensure concerted cell growth (size) and proliferation (number) in a given organ are poorly understood. Meanwhile, there is a urgent need to fully decipher the phenomena of tumor-related loss of Hippo signal and hyperactivation of YAP/TAZ, aiming to develop new therapeutic interventions. This Research Topic will focus on molecular elaboration of physiological and pathological roles of Hippo pathway in tissue development, tumorigenesis, and immune responses. Novel targeting strategies and pre-clinical studies related to the Hippo pathway are also warranted.
The scope of this Research Topic is to gather a comprehensive list of articles related to molecular dissection and translational investigation of both Hippo pathway and its co-regulation with metabolism and epigenetics. The Research Topic will cover various aspects of Hippo pathway ranging from tissue homeostasis and organ regeneration to tumorigenesis and immune responses, as well as development of novel cancer therapeutics by targeting Hippo pathway.
We welcome the submission of Original Research Articles, Reviews and Mini-reviews, including but not limited to the following topics:
• Mechanisms of how the extracellular stimuli such as growth factors and mechanical signals were sensed and transduced to initiate the Hippo signaling;
• Crosstalk of Hippo with other signaling pathways, metabolic and epigenetic factors at both cytoplasmic kinase-mediated and nuclear transcriptional factor-mediated levels;
• Research advancing our understanding in the complexity regulation of Hippo kinases including MST1/2 and LATS1/2 for their novel substrates and functions;
• Development of preclinical cancer therapeutics including but not limited to small molecular inhibitors and peptides that function by targeting Hippo signaling pathway;
• New insights into the regulatory roles of YAP/TAZ on chromatin activities and potential divergent functions between YAP and TAZ;
• Investigations concerning how Hippo signaling coordinate cell-cell interaction, cell growth and proliferation.
Keywords: Hippo signaling, Cancer biology, Tissue homeostasis, Immune response, Targeting strategy
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