The Crosstalk Between Hippo-YAP Pathway and Innate Immunity

Wang, Shuai; Zhou, Lili; Li, Ling; Meng, Xuli; Feng, Cuiping; Zhang, Suping; Zhou, Fangfang

doi:10.3389/fimmu.2020.00323

Cited by 110 publications

(86 citation statements)

References 132 publications

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“…The mammalian core kinases of the Hippo pathway comprise MST1/2 (ortholog of Drosophila Hippo/Hpo) 10 , SAV1 (also called WW45, salvador ortholog), LATS1/2 (Warts/Wts ortholog) 11 , 12 , and MOB1A/B (Mats ortholog) 13 . In addition, NDR1/2 (Trc ortholog) 14 and MAP4K (Happyhour/Hppy ortholog) 15 have been recently identified as novel components of the Hippo pathway 14 . The transcriptional co-activators YAP (also known as YAP1, Yorkie/Yki ortholog) 16 and TAZ (YAP paralog in mammals) 17 are the primary downstream effectors of the Hippo pathway 18 .…”

Section: The Hippo Pathwaymentioning

confidence: 99%

“…Increasing research in recent years has indicated an interplay between the Hippo and other pathways in intestinal regeneration, including the WNT 43 and Notch 44 pathway. Furthermore, the Hippo pathway has been suggested to be associated with inflammation, including the NF-κB pathways 45 , 46 and other components 9 , 47 , and also with immune-regulating pathways 15 .…”

Section: The Hippo Pathwaymentioning

confidence: 99%

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The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

et al. 2021

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Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder that primarily comprises Crohn’s disease (CD) and ulcerative colitis (UC). Owing to its increasing prevalence in Eastern countries and the intractable challenges faced during IBD treatment, extensive research on IBD has been carried out over the last few years. Although the precise aetiology of IBD is undefined, the currently accepted hypothesis for IBD pathogenesis considers it to be a combination of environment, genetic predisposition, gut microbiota, and abnormal immunity. A recently emerged signalling pathway, the Hippo pathway, acts as a key regulator of cell growth, tissue homoeostasis, organ size, and has been implicated in several human cancers. In the past few years, studies have revealed the importance of the Hippo pathway in gastrointestinal tract physiology and gastrointestinal diseases, such as colorectal cancer and IBD. However, the role of the Hippo pathway and its exact impact in IBD remains to be elucidated. This review summarises the latest scientific literature on the involvement of this pathway in IBD from the following perspectives that account for the IBD pathogenesis: intestinal epithelial cell regeneration, immune regulation, gut microbiota, and angiogenesis. A comprehensive understanding of the specific role of the Hippo pathway in IBD will provide novel insights into future research directions and clinical implications of the Hippo pathway.

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Section: The Hippo Pathwaymentioning

confidence: 99%

Section: The Hippo Pathwaymentioning

confidence: 99%

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

et al. 2021

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“…Inflammatory cytokines in the TME activate YAP/TAZ and sustain angiogenesis ( 334 – 338 ). Inflammatory cytokines activate AP-1 ( 339 ), which promotes oncogenic growth in conjunction with YAP/TAZ ( 171 ).…”

Section: Yap/taz Sustain Tumor Angiogenesis Through Feedback Mechanismentioning

confidence: 99%

Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

et al. 2021

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Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.

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“…For example, YAP was found to cooperate with TEA domain transcriptional factor (TEAD) and activate forkhead box D1 (FOXD1) expression, thus alleviating chondrocyte senescence and OA [129]. In a murine OA model, YAP activation by transgenic overexpression or deletion of the upstream inhibitory kinase Mst1/2 binding sites preserves articular cartilage integrity, whereas downregulation of YAP by inflammatory cytokines through TAK1-mediated phosphorylation promotes cartilage disruption [130,131]. Furthermore, YAP directly interacts with TAK1 and NF-κB signaling by inhibiting substrate TAK1 accessibility and reducing NF-κB-induced matrix-degrading enzyme expression and cartilage degradation during OA pathogenesis [130].…”

Section: Hippo Pathway-yap/taz Signalingmentioning

confidence: 99%

Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

Alexander

et al. 2020

Biology

187

115

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As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms.

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The Crosstalk Between Hippo-YAP Pathway and Innate Immunity

Cited by 110 publications

References 132 publications

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease

Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

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