ArticleOncotarget2017
Extracellular ATP, as an energy and phosphorylating molecule, induces different types of drug resistances in cancer cells through ATP internalization and intracellular ATP level increase.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 74 citations in OpenAlex.
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- VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's neurons.Science advances · 2026Article
- ABC Transporter Protein-mediated Multidrug Resistance in Breast Cancer and Development of Targeting Strategies.Recent patents on anti-cancer drug discovery · 2026Review
- From Oxidative Stress to Bioenergetic Remodeling: Translational Value and Clinical Implications of Exogenous ATP in PARP Inhibitor-Associated Liver Injury [Letter].Drug design, development and therapy · 2026Article
- Uncovering the molecular landscape of young-onset diffuse gastric cancer: A relieff-based feature selection analysis on RNA-Seq data.PloS one · 2026Article
- Potential Hepatoprotective Effects of Adenosine Triphosphate Against Olaparib-Induced Oxidative Liver Injury: An Experimental Rat Model.Drug design, development and therapy · 2026Article
- A novel pan class-I glucose transporter inhibitor DRB18 exhibits synergistic effects with paclitaxelbioRxiv : the preprint server for biology · 2025Article
- ATP increases murine neuroblastoma cell size through a PANX1- and macropinocytosis-dependent mechanism.Biology open · 2025Article
- P2 purinergic receptors regulate the progression of colorectal cancer.Purinergic signalling · 2025Review
- Molecular Interplay Between Non-Coding RNAs and Connexins and Its Possible Role in Cancer.International journal of molecular sciences · 2025Review
- Natural products reverse cancer multidrug resistance.Frontiers in pharmacology · 2024Review
- The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis.Oncology research · 2024Article
- Diverse temporal and spatial mechanisms work, partially through Stanniocalcin-1, V-ATPase and senescence, to activate the extracellular ATP-mediated drug resistance in human cancer cells.Frontiers in oncology · 2024Article
- ATP-responsive Mn(II)-basedChemical communications (Cambridge, England) · 2023Article
- An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential.Cancer cell international · 2023Review
- Purinergic signaling: Diverse effects and therapeutic potential in cancer.Frontiers in oncology · 2023Review
- Molecular and cellular paradigms of multidrug resistance in cancer.Cancer reports (Hoboken, N.J.) · 2022Review
- Cancer Stem Cell Formation Induced and Regulated by Extracellular ATP and Stanniocalcin-1 in Human Lung Cancer Cells and Tumors.International journal of molecular sciences · 2022Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are able to uptake extracellular ATP (eATP) via macropinocytosis to elevate intracellular ATP (iATP) levels, enhancing their survival in drug treatment. However, the involved drug resistance mechanisms are unknown. Here we investigated the roles of eATP as either an energy or a phosphorylating molecule in general drug resistance mediated by ATP internalization and iATP elevation. We report that eATP increased iATP levels and promoted drug resistance to various tyrosine kinase inhibitors (TKIs) and chemo-drugs in human cancer cell lines of five cancer types. In A549 lung cancer cells, the resistance was downregulated by macropinocytosis inhibition or siRNA knockdown of PAK1, an essential macropinocytosis enzyme. The elevated iATP upregulated the efflux activity of ABC transporters in A549 and SK-Hep-1 cells as well as phosphorylation of PDGFRα and proteins in the PDGFR-mediated Akt-mTOR and Raf-MEK signaling pathways in A549 cells. Similar phosphorylation upregulations were found in A549 tumors. These results demonstrate that eATP induces different types of drug resistance by eATP internalization and iATP elevation, implicating the ATP-rich tumor microenvironment in cancer drug resistance, expanding our understanding of the roles of eATP in the Warburg effect and offering new anticancer drug resistance targets.
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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.