Kaposi sarcoma-associated herpesvirus promotes tumorigenesis by modulating the Hippo pathway

Liu, Geoffrey; Yu, Fa-Xing; Kim, YC; Meng, Zhipeng; Naipauer, Julián; Dj, Looney; Liu, Xiaoyu; Gutkind, J. Silvio; Ea, Mesri; Kl, Guan

doi:10.1038/onc.2014.281

Cited by 65 publications

(58 citation statements)

References 67 publications

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“…PKA is also implicated as a widespread activator of LATS on other physiological stimuli [114]. GPCR-driven pathologies can be mediated via dysregulated YAP/TAZ [7,11–13,116] and examples of FDA-approved drugs targeting GPCRs modifying YAP/TAZ activity are known [10,117]. Several notable GPCR ligands play crucial roles in intestinal regeneration [118], development [119], and stem cell pluripotency [120,121] – biological processes where YAP and TAZ are known to be key mediators [6,74,107].…”

Section: Yap/taz As a Signaling Networkmentioning

confidence: 99%

YAP and TAZ: a nexus for Hippo signaling and beyond

Hansen

Moroishi

Guan

2015

Trends in Cell Biology

473

482

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The Hippo pathway is a potent regulator of cellular proliferation, differentiation, and tissue homeostasis. Here we review the regulatory mechanisms of the Hippo pathway and discuss the function of Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding domain (TAZ), the prime mediators of the Hippo pathway, in stem cell biology and tissue regeneration. We highlight their activities in both the nucleus and the cytoplasm and discuss their role as a signaling nexus and integrator of several other prominent signaling pathways such as the Wnt, G protein-coupled receptor (GPCR), epidermal growth factor (EGF), BMP/transforming growth factor beta (TGFβ), and Notch pathways.

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Section: Yap/taz As a Signaling Networkmentioning

confidence: 99%

YAP and TAZ: a nexus for Hippo signaling and beyond

Hansen

Moroishi

Guan

2015

Trends in Cell Biology

473

482

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“…Therefore, depending on the nature of downstream G proteins, GPCRs can either activate or inhibit the LATS kinase to stimulate or suppress YAP activity. Elevated GPCR expression or mutation of Gα proteins leads to aberrant YAP activation and exhibits strong disease implications Yu et al 2014;Liu et al 2015;Zhou et al 2015a). For example, estrogen acts through G protein-coupled estrogen receptor (GPER) to inhibit LATS and activate YAP/TAZ, indicating a possible role of YAP/TAZ activation by estrogen in breast cancer (Zhou et al 2015a).…”

Section: Soluble Factors and G-protein-coupled Receptors (Gpcrs)mentioning

confidence: 99%

Mechanisms of Hippo pathway regulation

2016

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The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

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“…In the nucleus, YAP/TAZ complex with transcription factors, most prominently the TEA domain family members (TEADs), to induce gene activation [6][7][8]. Hyperactivation of YAP/TAZ leads to overgrowth and cancer [9][10][11][12][13][14][15][16][17][18], but how YAP/TAZ confer cellular growth advantages is currently not well-understood [2].…”

Section: Introductionmentioning

confidence: 99%

The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1

et al. 2015

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YAP and TAZ are transcriptional co-activators and function as the major effectors of the Hippo tumor suppressor pathway, which controls cell growth, tissue homeostasis, and organ size. Here we show that YAP/TAZ play an essential role in amino acid-induced mTORC1 activation, particularly under nutrient-limiting conditions. Mechanistically, YAP/TAZ act via the TEAD transcription factors to induce expression of the high-affinity leucine transporter LAT1, which is a heterodimeric complex of SLC7A5 and SLC3A2. Deletion of YAP/TAZ abolishes expression of LAT1 and reduces leucine uptake. Re-expression of SLC7A5 in YAP/TAZ knockout cells restores leucine uptake and mTORC1 activation. Moreover, SLC7A5 knockout cells phenocopies YAP/TAZ knockout cells which exhibit defective mTORC1 activation in response to amino acids. We further demonstrate that YAP/TAZ act through SLC7A5 to provide cells with a competitive growth advantage. Our study provides molecular insight into the mechanism of YAP/TAZ target genes in cell growth regulation.

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Kaposi sarcoma-associated herpesvirus promotes tumorigenesis by modulating the Hippo pathway

Cited by 65 publications

References 67 publications

YAP and TAZ: a nexus for Hippo signaling and beyond

YAP and TAZ: a nexus for Hippo signaling and beyond

Mechanisms of Hippo pathway regulation

The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1

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