mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways

By P. Majumder, P. Febbo, Rachel Bikoff, R. Berger, Q. Xue, Louis M McMahon, J. Manola, J. Brugarolas, T. McDonnell, Todd R. Golub and 3 more. Nature Medicine, 2004

980 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/1504185446546eb4859a712053d970e850424259

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Citations in the corpus

Defining the Role of Hypoxia-Inducible Factor 1 in Cancer Biology and Therapeutics (2009, neutral): “…trastuzumab/Herceptin (Laughner et al., 2001) and the mTOR inhibitors rapamycin, temsirolimus/CCI-779 and everolimus/RAD-001 (Laughner et al., 2001; Majumder et al., 2004; Thomas et al., 2006), which all function by inhibiting mTOR-dependent translation of HIF-1a mRNA into protein (Laughner et…”
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity (2014, positive): “On the basis of observations that mTOR induction of glycolysis is mediated through activation of HIF-1a and stimulation of glycolytic enzymes (24) and that rapamycin inhibits HIF-1a expression (25), we assessed the effect of a HIF-1a inhibitor on monocyte training.”
Acetylation Targets the M2 Isoform of Pyruvate Kinase for Degradation through Chaperone-Mediated Autophagy and Promotes Tumor Growth (2011, neutral): “40) (Altenberg and Greulich, 2004; Majumder et al., 2004), which catalyzes the transfer of phosphate from phosphoenolpyruvate (PEP) to ADP, resulting in the formation of pyruvate and ATP.”
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. (2008, background): “During hypoxia, prolyl hydroxylation is inhibited by a process involving reactive oxygen species (ROS) generated in the mitochondria, resulting in stabilization of the HIF-1a protein and transcriptional activity of the HIF-1 complex (Brunelle et al., 2005; Guzyet al., 2005; Mansfield et al., 2005).”
The PTEN–PI3K pathway: of feedbacks and cross-talks (2008, background): “Interestingly, Akt overexpression leads to an mTORC1-dependent (rapamycin-sensitive) glucose metabolism signature, which underscores the major role of mTORC1 in AKT-driven tumorigenesis (Majumder et al., 2004).”
Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. (2008, background): “Evidence for the involvement in mTOR and Akt in tumorigenesis has been provided with animal models using either constitutively active Akt in association with rapamycin treatment (Majumder et al. 2004) or deletion of PTEN in combination with Akt knockout (Chen et al. 2006).”
Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer (2006, background): “Alternatively, additional molecular lesions such as expression of Bcl-2 could mitigate the response to inhibition of mTO”
A framework to identify physiological responses in microarray-based gene expression studies: selection and interpretation of biologically relevant genes. (2008, methodology): “This method enables detection of important pathways where all genes in a predefined set (for instance a GO category) change in a coordinated manner (29, 30).”
PKM2 Phosphorylates Histone H3 and Promotes Gene Transcription and Tumorigenesis (2012, positive): “This line of evidence establishes PKM2 as a unique and key regulator of cancer development by virtue of its coordination of ATP generation, macromolecular syntheses, and gene transcription via both metabolic and nonmetabolic functions.”
Activation of a metabolic gene regulatory network downstream of mTOR complex 1. (2010, background): “One of these studies concluded that myr-Akt induces most of the genes of glycolysis through increased HIF1α (Majumder et al., 2004), while the other found that myr-Akt induces many genes involved in lipid and cholesterol biosynthesis through increased SREBP1 and SREBP2 (Porstmann et al.”
The role of hypoxia-inducible factors in tumorigenesis (2008, background): “Although the exact mechanism by which mTOR regulates HIF activity is unclear, evidence suggests that it may have both transcriptional and post-translational effects on HIF.(57,58)”