ArticleActa pharmacologica Sinica2021
Inhibition of AXL enhances chemosensitivity of human ovarian cancer cells to cisplatin via decreasing glycolysis.
Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Hijacking of host PCNA by circovirus replication-associated protein to recruit POLD1 drives viral DNA replication and is inhibited by R428.PLoS pathogens · 2026Article
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- A fast-progressing orthotopic ovarian cancer model reveals synergistic antitumor effects of AXL-targeting nanobodies and Olaparib.Gynecologic oncology reports · 2025Article
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- AXL: shapers of tumor progression and immunosuppressive microenvironments.Molecular cancer · 2025Review
- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- Hallmarks of pancreatic cancer: spotlight on TAM receptors.EBioMedicine · 2024Review
- Application of single cell sequencing technology in ovarian cancer research (review).Functional & integrative genomics · 2024Review
- Identification of a novel DNA repair inhibitor using an in silico driven approach shows effective combinatorial activity with genotoxic agents against multidrug-resistant Escherichia coli.Protein science : a publication of the Protein Society · 2024Article
- Glucose metabolism reprogramming in gynecologic malignant tumors.Journal of Cancer · 2024Review
- Isoalantolactone Suppresses Glycolysis and Resensitizes Cisplatin-Based Chemotherapy in Cisplatin-Resistant Ovarian Cancer Cells.International journal of molecular sciences · 2023Article
- AXL in cancer: a modulator of drug resistance and therapeutic target.Journal of experimental & clinical cancer research : CR · 2023Review
- A Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) for ovarian cancer.Journal of translational medicine · 2023Article
- Receptor tyrosine kinase inhibitors in cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Axl and Vascular Endothelial Growth Factor Receptors Exhibit Variations in Membrane Localization and Heterogeneity Across Monolayer and Spheroid High-Grade Serous Ovarian Cancer Models.GEN biotechnology · 2023Article
- Research progress on the mechanism of glycolysis in ovarian cancer.Frontiers in immunology · 2023Review
- Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2.Cancers · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anexelekto (AXL), a member of the TYRO3-AXL-MER (TAM) family of receptor tyrosine kinases (RTK), is overexpressed in varieties of tumor tissues and promotes tumor development by regulating cell proliferation, migration and invasion. In this study, we investigated the role of AXL in regulating glycolysis in human ovarian cancer (OvCa) cells. We showed that the expression of AXL mRNA and protein was significantly higher in OvCa tissue than that in normal ovarian epithelial tissue. In human OvCa cell lines suppression of AXL significantly inhibited cell proliferation, and increased the sensitivity of OvCa cells to cisplatin, which also proved by nude mice tumor formation experiment. KEGG analysis showed that AXL was significantly enriched in the glycolysis pathways of cancer. Changes in AXL expression in OvCa cells affect tumor glycolysis. We demonstrated that the promotion effect of AXL on glycolysis was mediated by phosphorylating the M2 isoform of pyruvate kinase (PKM2) at Y105. AXL expression was significantly higher in cisplatin-resistant OvCa cells A2780/DDP compared with the parental A2780 cells. Inhibition of AXL decreased the level of glycolysis in A2780/DDP cells, and increased the cytotoxicity of cisplatin against A2780/DDP cells, suggesting that AXL-mediated glycolysis was associated with cisplatin resistance in OvCa. In conclusion, this study demonstrates for the first time that AXL is involved in the regulation of the Warburg effect. Our results not only highlight the clinical value of targeting AXL, but also provide theoretical basis for the combination of AXL inhibitor and cisplatin in the treatment of OvCa.
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