Differential IKK/NF-κB Activity Is Mediated by TSC2 through mTORC1 in PTEN-Null Prostate Cancer and Tuberous Sclerosis Complex Tumor Cells

@article{Gao2015DifferentialIA,
  title={Differential IKK/NF-$\kappa$B Activity Is Mediated by TSC2 through mTORC1 in PTEN-Null Prostate Cancer and Tuberous Sclerosis Complex Tumor Cells},
  author={Yu Gao and Ronald B. Gartenhaus and Rena G. Lapidus and Arif Hussain and Yanting Zhang and Xinghuan Wang and Han C. Dan},
  journal={Molecular Cancer Research},
  year={2015},
  volume={13},
  pages={1602 - 1614}
}
The serine/threonine protein kinase Akt plays a critical role in regulating proliferation, growth, and survival through phosphorylation of different downstream substrates. The mTOR is a key target for Akt to promote tumorigenesis. It has been reported that Akt activates mTOR through phosphorylation and inhibition of the tuberous sclerosis complex (TSC) protein TSC2. Previously, it was demonstrated that mTOR activates IKK/NF-κB signaling by promoting IκB kinase (IKK) activity downstream of Akt… Expand
Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Upregulates Glucose Transporter 1 Transcription via the mTORC1/NF-κB Signaling Pathways
TLDR
Evidence is provided that LMP1 upregulates Glut-1 transcription to control aerobic glycolysis and tumorigenic growth of NPC cells through mTORC1/NF-κB signaling. Expand
The anticancer effects of curcumin via targeting the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.
TLDR
Evidence revealed that curcumin downregulates the E3-ubiquitin ligases NEDD4, neural precursor cell-expressed developmentally downregulated 4, which are frequently overexpressed in a wide range of cancers and degrades the phosphatase and tensin homolog, which is a negative regulator of mTORC1. Expand
Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention
TLDR
The function of the PI3K/Akt/mTOR pathway, the consequence of its dysregulation, and the development of mTOR inhibitors, either as an individual substance or in combination with other agents, and their clinical implications are discussed. Expand
Characterization of CADD522, a small molecule that inhibits RUNX2-DNA binding and exhibits antitumor activity
TLDR
The results suggest several potential mechanisms by which CADD522 exerts an inhibitory function on RUNX2-DNA binding; interference with RUNx2 for the DNA binding pocket, inhibition of glucose uptake leading to cell cycle arrest, down-regulation of CBF-β, and reduction of S451-RUNX2 phosphorylation. Expand
Arenobufagin Inhibits the Phosphatidylinositol 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin Pathway and Induces Apoptosis and Autophagy in Pancreatic Cancer Cells.
TLDR
Arenobufagin inhibits tumor growth in vivo and in vitro and its molecular mechanism may involve induction of autophagy and apoptosis through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Expand
Proscillaridin A induces apoptosis and suppresses non-small-cell lung cancer tumor growth via calcium-induced DR4 upregulation
TLDR
Results suggest that P.A is a promising anti-cancer therapeutic candidate for NSCLC and shows less pharmaceutical toxicity than Afatinib. Expand
The oncometabolite 2-hydroxyglutarate inhibits microglial activation via the AMPK/mTOR/NF-κB pathway
TLDR
Results show that oncometabolite 2HG inhibits microglial activation through affecting AMPK/mTOR/NF-κB signaling pathway and provide evidence that on cometabolic product 2-hydroxyglutarate (2HG) may regulate glioma development via modulating microglia activation in tumor microenvironment. Expand
Pretreatment of Anthocyanin from the Fruit of Vitis coignetiae Pulliat Acts as a Potent Inhibitor of TNF-α Effect by Inhibiting NF-κB-Regulated Genes in Human Breast Cancer Cells
TLDR
It is demonstrated that the anthocyanins isolated from the fruits of Vitis coignetiae Pulliat acts as an inhibitor of TNF-α induced NF-κB activation, and subsequent downstream molecules involved in cancer proliferation, invasion, adhesion, angiogenesis, and thus have anti-metastatic activities in MCF-7 breast cancer cells. Expand
Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms
TLDR
The results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. Expand
Ginkgo biloba Exocarp Extract Inhibits the Metastasis of B16-F10 Melanoma Involving PI3K/Akt/NF-κB/MMP-9 Signaling Pathway
  • Chenjie Cao, Ya Su, +5 authors A. Xu
  • Chemistry, Medicine
  • Evidence-based complementary and alternative medicine : eCAM
  • 2018
TLDR
Results indicate that GBEE can inhibit the metastasis of B16-F10 melanoma via multiple links and the molecular mechanism involved the regulation of PI3K/Akt/NF-κB/MMP-9 signaling pathway. Expand
...
1
2
...

References

SHOWING 1-10 OF 76 REFERENCES
Regulation of Mammalian Target of Rapamycin Activity in PTEN-Inactive Prostate Cancer Cells by IκB Kinase α
TLDR
An involvement of the IκB kinase (IKK) pathway, associated with nuclear factor-κB activation, in controlling mTOR activity is explored and results indicate a novel role for IKKα in controllingmTOR function in cancer cells with constitutive Akt activity. Expand
Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK.
TLDR
It is shown that mTOR downstream from Akt controls NF-kappaB activity in PTEN-null/inactive prostate cancer cells via interaction with and stimulation of IKK, and the mTOR-associated protein Raptor is required for the ability of Akt to induce NF- kappa B activity. Expand
Essential role of tuberous sclerosis genes TSC1 and TSC2 in NF-kappaB activation and cell survival.
TLDR
Results provide evidence for a crosstalk between the TSC/Rheb/mTOR pathway and the NF-kappaB induction pathways and indicate that NF- kappaB functions as an important survival factor that regulates TSC2-dependent cell survival. Expand
Regulation of mammalian target of rapamycin activity in PTEN-inactive prostate cancer cells by I kappa B kinase alpha.
TLDR
The experiments show that IKK alpha controls mTOR kinase activity in Akt-active, PTEN-null prostate cancer cells, with less involvement by IKK beta. Expand
A complex interplay between Akt, TSC2 and the two mTOR complexes.
TLDR
The present review discusses the current understanding of the increasingly complex functional interactions between Akt, the TSC1-TSC2 complex and mTOR, which are fundamentally important players in a large variety of human diseases. Expand
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
TLDR
It is shown that TSC1–TSC2 inhibits the p70 ribosomal protein S6 kinase 1 and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation) and these functions are mediated by inhibition of the mammalian target of rapamycin (mTOR). Expand
Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2.
TLDR
Evidence is provided that TSC1/2 is a GAP for the small GTPase Rheb and that insulin-mediated RheB activation is PI3K dependent and that Rhe b overexpression induces S6K1 phosphorylation and inhibits PKBosphorylation, as do loss-of-function mutations in TSC 1/2. Expand
The TSC1-TSC2 Complex Is Required for Proper Activation of mTOR Complex 2
TLDR
It is demonstrated that the TSC1-TSC2 complex inhibits m TORC1 and activates mTORC2, which through different mechanisms promotes Akt activation. Expand
Inappropriate Activation of the TSC/Rheb/mTOR/S6K Cassette Induces IRS1/2 Depletion, Insulin Resistance, and Cell Survival Deficiencies
TLDR
It is demonstrated herein that constitutive activation of the Rheb/mTOR/S6K cassette, whether by genetic deletion of TSC1 or TSC2 or by ectopic expression of RheB, is sufficient to induce insulin resistance. Expand
Phosphorylation and Functional Inactivation of TSC2 by Erk Implications for Tuberous Sclerosisand Cancer Pathogenesis
TLDR
The findings position the Ras/MAPK pathway upstream of the TSC complex and suggest that Erk may modulate mTOR signaling and contribute to disease progression through phosphorylation and inactivation of TSC2. Expand
...
1
2
3
4
5
...