Inhibition of the LKB1–AMPK pathway by the Epstein–Barr virus‐encoded LMP1 promotes proliferation and transformation of human nasopharyngeal epithelial cells

@article{Lo2013InhibitionOT,
  title={Inhibition of the LKB1–AMPK pathway by the Epstein–Barr virus‐encoded LMP1 promotes proliferation and transformation of human nasopharyngeal epithelial cells},
  author={Angela Kwok Fung Lo and Kwok Wai Lo and Chun-Wai Ko and Lawrence S Young and Christopher W. Dawson},
  journal={The Journal of Pathology},
  year={2013},
  volume={230}
}
The association of Epstein–Barr virus (EBV) infection with the development of nasopharyngeal carcinoma (NPC) is well established. Latent membrane protein 1 (LMP1), the major oncogene encoded by EBV, is believed to play a crucial role in NPC pathogenesis by virtue of its ability to constitutively activate multiple cell signalling pathways. The LKB1–AMPK pathway is a master regulator of cellular metabolism that, via modulation of energy metabolism, has tumour suppressor activity. In this study we… Expand
Activation of the FGFR1 signalling pathway by the Epstein–Barr virus‐encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells
TLDR
It is demonstrated that LMP1‐mediated FGFR1 activation contributes to aerobic glycolysis and transformation of epithelial cells, thereby implicating FGF2/FGFR1 signalling activation in the EBV‐driven pathogenesis of NPC. Expand
EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma.
TLDR
The data revealed a new mechanism of LMP1-mediated radioresistance and provided a mechanistic rationale in support of the use of AMPK activators for facilitating NPC radiotherapy. Expand
Activation of sterol regulatory element‐binding protein 1 (SREBP1)‐mediated lipogenesis by the Epstein–Barr virus‐encoded latent membrane protein 1 (LMP1) promotes cell proliferation and progression of nasopharyngeal carcinoma
TLDR
It is demonstrated that LMP1 activation of SREBP1‐mediated lipogenesis promotes tumor cell growth and is involved in EBV‐driven NPC pathogenesis and the therapeutic potential of utilizing lipogenesis inhibitors in the treatment of locally advanced or metastatic NPC is revealed. Expand
Upregulation of GLS1 Isoforms KGA and GAC Facilitates Mitochondrial Metabolism and Cell Proliferation in Epstein–Barr Virus Infected Cells
TLDR
The results suggest that c-Myc-dependent regulation of KGA and GAC enhances mitochondrial functions to support the rapid proliferation of theEBV-infected cells, and these metabolic processes could be therapeutically exploited by targeting KGA/GAC and GLUD1 to prevent EBV-associated cancers. Expand
Epstein-barr virus induction of the hedgehog signalling pathway imposes a stem cell-like phenotype on human epithelial cells – implications for the pathogenesis of nasopharyngeal carcinoma
TLDR
It is demonstrated that constitutive engagement of the HH pathway in EBV-infected epithelial cells in vitro induces the expression of a number of stemness-associated genes and imposes stem-like characteristics. Expand
Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-κB pathway.
TLDR
The findings indicated the newly identified miR-BART13/NKIRAS2/NF-κB signaling axis may provide further insights into better understanding of NPC initiation and development, and targeting of this pathway could be further studied as a therapeutic strategy for NPC patients. Expand
AMP-activated Kinase (AMPK) Promotes Innate Immunity and Antiviral Defense through Modulation of Stimulator of Interferon Genes (STING) Signaling*
TLDR
The host protein Stimulator of Interferon Genes (STING) has been shown to be essential for recognition of both viral and intracellular bacterial pathogens, but its regulation remains unclear, and it is postulated that AMPK participates in STING activation. Expand
Repression of integrin-linked kinase by antidiabetes drugs through cross-talk of PPARγ- and AMPKα-dependent signaling: role of AP-2α and Sp1.
TLDR
It is shown that antidiabetes drugs rosiglitazone and metformin inhibit NPC cell growth through reducing the expression of integrin-linked kinase (ILK). Expand
CRISPR/Cas9-mediated LMP1 knockout inhibits Epstein-Barr virus infection and nasopharyngeal carcinoma cell growth
TLDR
Investigation of latent membrane protein 1 (LMP1) regulation of nasopharyngeal carcinoma CNE-2 cell growth and the effects of LMP1-knockout with CRISPR/Cas9 on Epstein-Barr virus infection and NPC cell growth confirmed the L MP1-mediated promotion of NPC cell Growth. Expand
DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target
TLDR
DENV infection increases HMGCR activity through AMPK inactivation leading to higher cholesterol levels in endoplasmic reticulum necessary for replicative complexes formation and identifies new potential antiviral targets for DENV replication. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 45 REFERENCES
Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition
TLDR
It is demonstrated that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1, and evidence is provided that L MP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation. Expand
Epstein–Barr virus latent membrane protein 1 (LMP1) upregulates Id1 expression in nasopharyngeal epithelial cells
TLDR
It is shown that induction of Id1 by LMP1 was dependent on its NF-κB activation domain at the carboxy-terminal region, CTAR1 and CTAR2 and may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV and may promote their malignant transformation. Expand
Activation of the cJun N-terminal kinase (JNK) pathway by the Epstein-Barr virus-encoded latent membrane protein 1 (LMP1)
TLDR
It is demonstrated that stable or transient expression of the LMP1 prototype from B95.8 in cells of epithelial or B cell origin activates the c-Jun N-terminal kinase (JNK) pathway, an effect which was found to be mediated through CTAR2 but not CTAR1. Expand
The significance of LMP1 expression in nasopharyngeal carcinoma.
TLDR
The frequent expression of LMP1 in undifferentiated nasopharyngeal carcinoma (NPC) points to a role for this viral oncoprotein as a key effector molecule in NPC pathogenesis. Expand
The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC).
TLDR
The effects of LMP1 and LMP2 on various aspects of epithelial cell behaviour are reviewed highlighting key aspects that may contribute to the pathogenesis of NPC. Expand
Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation.
TLDR
It is found that in melanoma cells with the B-RAF V600E mutation LKB1 is phosphorylated by ERK and Rsk, two kinases downstream of B- RAF, and that this phosphorylation compromises the ability of L KB1 to bind and activate AMPK. Expand
Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice.
TLDR
The results demonstrate the potential of AMPK activators, such as clinically approved metformin, as anticancer agents, which will suppress tumour development by triggering a physiological signalling pathway that potently inhibits cell growth. Expand
Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) Activates the Phosphatidylinositol 3-Kinase/Akt Pathway to Promote Cell Survival and Induce Actin Filament Remodeling*
TLDR
It is shown that LMP1 can activate phosphatidylinositol 3-kinase (PI3K), a lipid kinase responsible for activating a diverse range of cellular processes in response to extracellular stimuli, and suggests that this pathway contributes both to the oncogenicity of this molecule and its role in the establishment of persistent EBV infection. Expand
Latent membrane protein 1 of Epstein-Barr virus regulates p53 phosphorylation through MAP kinases.
TLDR
Results strongly suggest that MAP kinases have a direct role in LMP1-induced phosphorylation of p53 at multiple sites, which provide a novel view for us to understand the mechanism of the activation of p 53 in the carcinogenesis of nasopharyngeal carcinoma. Expand
Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells.
TLDR
It is shown that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia-mutated (ATM) tumor suppressor and concluded that B mi-1 contributes to L MP1-induced oncogenesis in HL. Expand
...
1
2
3
4
5
...