ArticleMolecular and cellular biology2009
Mutation of the Rb1 pathway leads to overexpression of mTor, constitutive phosphorylation of Akt on serine 473, resistance to anoikis, and a block in c-Raf activation.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- A Phase 0 Trial of Ribociclib in Recurrent Glioblastoma Patients Incorporating a Tumor Pharmacodynamic- and Pharmacokinetic-Guided Expansion Cohort.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- B4GALNT4-Mediated Glycosylation of PDK1 Activates the PI3K-AKT Signaling Pathway to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Construction of a novel anoikis-related prognostic model and analysis of its correlation with infiltration of immune cells in neuroblastoma.Frontiers in immunology · 2023Article
- β-elemene suppresses tumor metabolism and stem cell-like properties of non-small cell lung cancer cells by regulating PI3K/AKT/mTOR signaling.American journal of cancer research · 2022Article
- Paracrine effects of intraocularly implanted cells on degenerating retinas in mice.Stem cell research & therapy · 2020Article
- Palbociclib improves cardiac dysfunction in diabetic cardiomyopathy by regulating Rb phosphorylation.American journal of translational research · 2019Article
- Combined CDK4/6 and mTOR Inhibition Is Synergistic against Glioblastoma via Multiple Mechanisms.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor.Journal of dental research · 2017Article
- Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies.World journal of stem cells · 2016Review
- High and low dose radiation effects on mammary adenocarcinoma cells - an epigenetic connection.Oncoscience · 2016Article
- mTORC1 maintains the tumorigenicity of SSEA-4(+) high-grade osteosarcoma.Scientific reports · 2015Article
- An Rb1-dependent amplification loop between Ets1 and Zeb1 is evident in thymocyte differentiation and invasive lung adenocarcinoma.BMC molecular biology · 2015Article
- The ZEB1 transcription factor acts in a negative feedback loop with miR200 downstream of Ras and Rb1 to regulate Bmi1 expression.The Journal of biological chemistry · 2014Article
- Methylene blue promotes quiescence of rat neural progenitor cells.Frontiers in cellular neuroscience · 2014Article
- Increased mammalian target of rapamycin complex 2 signaling promotes age-related decline in CD4 T cell signaling and function.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Sequential inductions of the ZEB1 transcription factor caused by mutation of Rb and then Ras proteins are required for tumor initiation and progression.The Journal of biological chemistry · 2013Article
- Article
- Ginsenoside rb1 reduces isoproterenol-induced cardiomyocytes apoptosis in vitro and in vivo.Evidence-based complementary and alternative medicine : eCAM · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Atk can be activated by two independent phosphorylation events. Growth factor-dependent phosphorylation of threonine 308 (Akt-308) by phosphatidylinositol 3-kinase-dependent PDK1 leads to activation of mammalian target of rapamycin (mTor) complex 1 (TORC1) and stimulation of protein synthesis. Phosphorylation on serine 473 (Akt-473) is catalyzed by mTor in a second complex (TORC2), and Akt-473 phosphorylates Foxo3a to inhibit apoptosis. Accumulation of both phosphorylated forms of Akt is frequent in cancer, and TORC2 activity is required for progression to prostate cancer with Pten mutation. Here, we link Akt-473 to the Rb1 pathway and show that mTor is overexpressed with loss of the Rb1 family pathway. This leads to constitutive Akt-473 and, in turn, phosphorylation of Foxo3a and resistance to cell adhesion-dependent apoptosis (anoikis). Additionally, Akt-473 accumulation blocks c-Raf activation, thereby preventing downstream Erk activation. This block cannot be overcome by constitutively active Ras, and it also prevents induction of the Arf tumor suppressor by Ras. These studies link inactivation of the Rb1 pathway, a hallmark of cancer, to accumulation of Akt-473, resistance to anoikis, and a block in c-Raf/Erk activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.