Hippo Pathway in Mammalian Adaptive Immune System

Yamauchi, Takayoshi; Moroishi, Toshiro

doi:10.3390/cells8050398

Cited by 65 publications

(44 citation statements)

References 124 publications

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“…A recent study has shown that in Drosophila the Hippo signaling pathway regulates innate immune response and is activated downstream of the Toll like receptor (TLR) pathway to regulate production of anti-microbial peptides ( 21 ). Emerging evidence has indicated that YAP is also implicated in the regulation of macrophage immune responses ( 46 ). Zhou et al show that depletion of YAP in macrophages relieves pro-inflammatory responses in inflammatory bowel disease (IBD) via enhancing macrophage M2 polarization and suppressing IL6 production ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB Activation via GPR81-Mediated Signaling

et al. 2020

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Recent evidence from cancer research indicates that lactate exerts a suppressive effect on innate immune responses in cancer. This study investigated the mechanisms by which lactate suppresses macrophage pro-inflammatory responses. Macrophages [Raw 264.7 and bone marrow derived macrophages (BMDMs)] were treated with LPS in the presence or absence of lactate. Pro-inflammatory cytokines, NF-κB and YAP activation and nuclear translocation were examined. Our results show that lactate significantly attenuates LPS stimulated macrophage TNF-α and IL-6 production. Lactate also suppresses LPS stimulated macrophage NF-κB and YAP activation and nuclear translocation in macrophages. Interestingly, YAP activation and nuclear translocation are required for LPS stimulated macrophage NF-κB activation and TNFα production. Importantly, lactate suppressed YAP activation and nuclear translocation is mediated by GPR81 dependent AMKP and LATS activation which phosphorylates YAP, resulting in YAP inactivation. Finally, we demonstrated that LPS stimulation induces an interaction between YAP and NF-κB subunit p65, while lactate decreases the interaction of YAP and NF-κB, thus suppressing LPS induced pro-inflammatory cytokine production. Our study demonstrates that lactate exerts a previously unknown role in the suppression of macrophage pro-inflammatory cytokine production via GPR81 mediated YAP inactivation, resulting in disruption of YAP and NF-κB interaction and nuclear translocation in macrophages.

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Section: Discussionmentioning

confidence: 99%

Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB Activation via GPR81-Mediated Signaling

et al. 2020

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“…Although EGFR acquires drug resistance to TKI via the T790M mutation, TEAD inhibition effectively reduces the viability of TKI-resistant lung adenocarcinoma cells [166,167]. TEAD also contributes to the immune escape of NSCLC cells by directly transcribing PD-L1 , which, in turn, causes CD8 + T cell exhaustion [43,168]. Furthermore, TEAD increases EGFR expression by directly binding to the EGFR promotor, which induces tumorigenesis and drug resistance in esophageal cancer [39].…”

Section: Teads As Mediators Of Cancer Genesmentioning

confidence: 99%

Regulation of TEAD Transcription Factors in Cancer Biology

Huh

Kim

Jeong

et al. 2019

Cells

188

157

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Transcriptional enhanced associate domain (TEAD) transcription factors play important roles during development, cell proliferation, regeneration, and tissue homeostasis. TEAD integrates with and coordinates various signal transduction pathways including Hippo, Wnt, transforming growth factor beta (TGFβ), and epidermal growth factor receptor (EGFR) pathways. TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway. Therefore, most studies are focused on the Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and Hippo-independent regulators and regulations governing TEAD only emerged recently. Deregulation of the TEAD transcriptional output plays important roles in tumor progression and serves as a prognostic biomarker due to high correlation with clinicopathological parameters in human malignancies. In addition, discovering the molecular mechanisms of TEAD, such as post-translational modifications and nucleocytoplasmic shuttling, represents an important means of modulating TEAD transcriptional activity. Collectively, this review highlights the role of TEAD in multistep-tumorigenesis by interacting with upstream oncogenic signaling pathways and controlling downstream target genes, which provides unprecedented insight and rationale into developing TEAD-targeted anticancer therapeutics.

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“…48,49) In contrast, aberrant activation of the Hippo pathway impairs tissue development, stem cell maintenance, and differentiation. 50) In addition to those cell-autonomous functions, recent studies revealed that the Hippo pathway also mediates non-cell autonomous functions, such as cell competition [51][52][53][54][55] and immune responses, [56][57][58][59][60] which play a pivotal role in the homeostatic control of multicellular organisms. 61,62) Thus, collectively, the Hippo intracellular signaling pathway acts as a nexus and integrator for multiple signals from the cellular microenvironment, regulat-ing multiple aspects of cell biology, and thereby contributing to cell-fate determination 63) (Fig.…”

Section: Introductionmentioning

confidence: 99%

The Emerging Link between the Hippo Pathway and Non-coding RNA

Shimoda

Moroishi

2020

Biological & Pharmaceutical Bulletin

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The Hippo intracellular signaling pathway plays a pivotal role in cell fate determination. Although previous studies have identified many components of the Hippo pathway, the whole picture of the Hippo network is just beginning to be delineated. Recent discoveries in the past decade have shed light on a newly discovered signaling network where the Hippo pathway interplays with several types of non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs, to mediate diverse biological processes. Those non-coding RNAs communicate with each other to maintain cellular homeostasis. In this review article, we summarize the current and emerging understanding of the roles of non-coding RNAs in the regulation of and by the Hippo pathway.

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Hippo Pathway in Mammalian Adaptive Immune System

Cited by 65 publications

References 124 publications

Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB Activation via GPR81-Mediated Signaling

Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB Activation via GPR81-Mediated Signaling

Regulation of TEAD Transcription Factors in Cancer Biology

The Emerging Link between the Hippo Pathway and Non-coding RNA

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