mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt.

By K. O'reilly, F. Rojo, Q. She, D. Solit, Gordon B. Mills, Debra L. Smith, H. Lane, F. Hofmann, D. Hicklin, D. Ludwig and 2 more. Cancer Research, 2006

2,588 citations recorded by the source corpus.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/905f4c2bc2cb436e91e24eb36e923233c064768e

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Citations in the corpus

Targeting PI3K/Akt signal transduction for cancer therapy (2021, background): “mTORC1 inhibitors tend to activate the PI3K signaling pathway through feedback inhibition.(209) Therefore, the advantages of dual pan-PI3K and mTOR inhibitors in inhibiting feedback inhibition are highlighted, and they have obvious therapeutic advantages.”
Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism (2007, result): “Our results are consistent with recent reports that rapamycin induces Akt activation in human nonsmall-cell lung cancer and breast cancer cell lines (Sun et al., 2005; O’Reilly et al., 2006).”
Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. (2008, result): “These experiments show that phosphorylated Akt (S473) is increased following rapamycin treatment, consistent with the findings of others (O’Reilly et al. 2006; Shah and Hunter 2006), which show that S6K feeds back to block IRS-1 through phosphorylation.”
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity (2008, background): “Due to a negative feedback loop involving the phosphorylation of p70S6K, inhibition of mTORC1activity alone could result in the enhanced activation of the PI3K axis (49).”
AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity (2011, positive): “It is increasingly clear that dysregulation of mitogenic signaling by constitutively activated oncoproteins in cancer cells drives high levels of feedback inhibition of the signaling network (Courtois-Cox et al., 2006; O'Reilly et al., 2006; Pratilas et al., 2009).”
Rapamycin passes the torch: a new generation of mTOR inhibitors (2011, positive): “Diseased tissue samples taken from patients with colon or breast cancer after 4 weeks of treatment with everolimus showed higher levels of activated AKT compared to pretreatment sample”
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism (2006, background): “In fact, this feedback has now been observed in certain cancers treated with rapamycin analogue”
mTOR: from growth signal integration to cancer, diabetes and ageing (2010, background): “4Ba ), the inhibition of which leads to a severe upregulation of PI3K signalling and provides important pro-survival and proliferative signals through Akt and other AGC kinase”
The PI3K/AKT Pathway as a Target for Cancer Treatment. (2016, background): “The release of this feedback mechanism results in IRS-1-mediated reactivation of AKT, which, in turn, counteracts and limits the antitumor effect of rapalogs (40).”
The PI3K pathway in human disease (2017, positive): “In the absence of mTORC2 inhibition, loss of this negative feedback leads to AKT hyperactivation (O’Reilly et al., 2006).”