ArticleMolecular biology of the cell2002
Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01822015 (A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy), which is not on this map. Cited by 271 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Pilot, Pharmacodynamic Correlate Trial of Sirolimus in Combination With Chemotherapy (Idarubicin, Cytarabine) for the Treatment of Newly Diagnosed Acute Myelogenous Leukemia
Who cites it
271 citing papers in PubMed, 2 syntheses or guidelines pooled it, 584 citations in OpenAlex.
- Prognostic value of skeletal muscle mass during tyrosine kinase inhibitor (TKI) therapy in cancer patients: a systematic review and meta-analysis.Internal and emergency medicine · 2021Pooled it
- Genetic polymorphisms of mTOR and cancer risk: a systematic review and updated meta-analysis.Oncotarget · 2016Pooled it
- The chemokine CCL5 regulates glucose uptake and AMP kinase signaling in activated T cells to facilitate chemotaxis.The Journal of biological chemistry · 2012Trial
- Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.British journal of cancer · 2012Trial
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Tissue Immunometabolism in Autoimmunity.European journal of immunology · 2026Review
- TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence.The EMBO journal · 2025Article
- Metabolic reprogramming by PRDM16 drives cytarabine resistance in acute myeloid leukemia.Haematologica · 2025Article
- Rewiring cancer metabolism: oncogenic signaling pathways and targeted therapeutics.Science China. Life sciences · 2025Review
- Time Does Matter: The Cellular Response to Resveratrol Varies Depending on the Exposure Duration.International journal of molecular sciences · 2025Article
- Paradoxical Effect of Myosteatosis on the Immune Checkpoint Inhibitor Response in Metastatic Renal Cell Carcinoma.Journal of cachexia, sarcopenia and muscle · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- The relationship between systemic therapies and low skeletal muscle mass in patients with intermediate and advanced hepatocellular carcinoma.Frontiers in immunology · 2025Article
- CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy.Molecular biology of the cell · 2025Article
- Application of mesenchymal stem cells in liver fibrosis and regeneration.Liver research (Beijing, China) · 2024Review
- Oncogenic Control of Metabolism.Cold Spring Harbor perspectives in medicine · 2024Review
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- The stress sensor GCN2 differentially controls ribosome biogenesis in colon cancer according to the nutritional context.Molecular oncology · 2024Article
- Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation.Nature communications · 2024Article
- Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver.Nature communications · 2024Article
211 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In multicellular organisms, constituent cells depend on extracellular signals for growth, proliferation, and survival. When cells are withdrawn from growth factors, they undergo apoptosis. Expression of constitutively active forms of the serine/threonine kinase Akt/PKB can prevent apoptosis upon growth factor withdrawal. Akt-mediated survival depends in part on the maintenance of glucose metabolism, suggesting that reduced glucose utilization contributes to growth factor withdrawal-induced death. However, it is unclear how restricting access to extracellular glucose alone would lead to the metabolic collapse observed after growth factor withdrawal. We report herein that growth factor withdrawal results in the loss of surface transporters for not only glucose but also amino acids, low-density lipoprotein, and iron. This coordinated decline in transporters and receptors for extracellular molecules creates a catabolic state characterized by atrophy and a decline in the mitochondrial membrane potential. Activated forms of Akt maintained these transporters on the cell surface in the absence of growth factor through an mTOR-dependent mechanism. The mTOR inhibitor rapamycin diminished Akt-mediated increases in cell size, mitochondrial membrane potential, and cell survival. These results suggest that growth factors control cellular growth and survival by regulating cellular access to extracellular nutrients in part by modulating the activity of Akt and mTOR.
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Registered trials
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.