ArticleCancers2019
Rac-Mediated Macropinocytosis of Extracellular Protein Promotes Glucose Independence in Non-Small Cell Lung Cancer.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- A systematic review of omics discovery studies to identify pertinent metabolic pathways for locally advanced rectal cancer in response to neoadjuvant chemoradiotherapy.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Advances in miRNA-Mediated Bidirectional Crosstalk and Immune Evasion Mechanisms Between Lung Cancer Cells and CD8International journal of molecular sciences · 2026Review
- Targeting macropinocytosis for cancer therapy.Nature reviews. Cancer · 2026Review
- Targeted Metabolomic Serum Analysis of Patients with High and Low Risk of Endometrial Cancer Recurrence and Positive and Negative Lymph Node Status.Metabolites · 2025Article
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Emerging role of the TCA cycle and its metabolites in lung disease.Frontiers in physiology · 2025Review
- CARMIL1-AA selectively inhibits macropinocytosis while sparing autophagy.Molecular biology of the cell · 2025Article
- Synthesis and Biological Evaluation of Fluorine-18 and Deuterium Labeled l-Fluoroalanines as Positron Emission Tomography Imaging Agents for Cancer Detection.Journal of medicinal chemistry · 2024Article
- Alveolar-capillary endocytosis and trafficking in acute lung injury and acute respiratory distress syndrome.Frontiers in immunology · 2024Review
- Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts.Journal of experimental & clinical cancer research : CR · 2023Article
- Inhibition of Macropinocytosis Enhances the Sensitivity of Osteosarcoma Cells to Benzethonium Chloride.Cancers · 2023Article
- Metabolic signatures of lymphangioleiomyomatosis in biofluids: nuclear magnetic resonance (NMR)-based metabonomics of blood plasma: a case-control study.Annals of translational medicine · 2023Article
- ATM inhibition drives metabolic adaptation via induction of macropinocytosis.The Journal of cell biology · 2023Article
- Unraveling the Rewired Metabolism in Lung Cancer Using Quantitative NMR Metabolomics.International journal of molecular sciences · 2022Review
- Revealing macropinocytosis using nanoparticles.Molecular aspects of medicine · 2022Review
- The Role and Therapeutic Potential of Macropinocytosis in Cancer.Frontiers in pharmacology · 2022Review
- From Transcriptomics, Metabolomics to Functional Studies: Extracellular ATP Induces TGF-β-Like Epithelial Mesenchymal Transition in Lung Cancer Cells.Frontiers in oncology · 2022Article
- Amino acid metabolism as a therapeutic target in cancer: a review.Amino acids · 2021Review
- Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment.Nature reviews. Cancer · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells can adapt to nutrient poor conditions by rewiring their metabolism and using alternate fuel sources. Identifying these adaptive metabolic pathways may provide novel targets for cancer therapy. Here, we identify a subset of non-small cell lung cancer (NSCLC) cell lines that survive in the absence of glucose by internalizing and metabolizing extracellular protein via macropinocytosis. Macropinocytosis is increased in these glucose independent cells, and is regulated by phosphoinositide 3-kinase (PI3K) activation of Rac-Pak signaling. Furthermore, inhibition of Rac-dependent macropinocytosis blocks glucose-independent proliferation. We find that degradation of internalized protein produces amino acids, including alanine, which generates TCA cycle and glycolytic intermediates in the absence of glucose. In this process, the conversion of alanine to pyruvate by alanine transaminase 2 (ALT2) is critical for survival during glucose starvation. Collectively, Rac driven macropinocytosis of extracellular protein is an adaptive metabolic pathway used by a subset of lung cancers to survive states of glucose deprivation, and may serve as a potential drug target for cancer therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.