ArticleJournal of experimental & clinical cancer research : CR2022
Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Advances in understanding the mechanisms underlying acquired resistance to third-generation tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Review
- Royal jelly and doxorubicin suppressed tumor cells in the xenograft model of lung cancer via the STAT3/FOXM1/ATG7 signaling pathways in athymic nude mice: a biochemical, immunohistochemically and molecular approach.Toxicology research · 2025Article
- PD-L1 induces autophagy and primary resistance to EGFR-TKIs in EGFR-mutant lung adenocarcinoma via the MAPK signaling pathway.Cell death & disease · 2024Article
- METTL14 inhibits the proliferation, migration and invasion of prostate cancer cells by increasing m6A methylation of CDK4.Translational andrology and urology · 2024Article
- FOXM1 mediates methotrexate resistance in osteosarcoma cells by promoting autophagy.Acta biochimica et biophysica Sinica · 2024Article
- Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging.Journal of nanobiotechnology · 2024Article
- Photonanozyme-Kras-ribosome combination treatment of non-small cell lung cancer after COVID-19.Frontiers in immunology · 2024Review
- AUF1-induced circular RNA hsa_circ_0010467 promotes platinum resistance of ovarian cancer through miR-637/LIF/STAT3 axis.Cellular and molecular life sciences : CMLS · 2023Article
- RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer.JCI insight · 2023Article
- Gold-nanoparticle-embedded hydrogel droplets with enhanced fluorescence for imaging and quantification of proteins in cells.Mikrochimica acta · 2023Article
- The Potential of Senescence as a Target for Developing Anticancer Therapy.International journal of molecular sciences · 2023Review
- Inhibition of autophagy; an opportunity for the treatment of cancer resistance.Frontiers in cell and developmental biology · 2023Review
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14 authors at 2 institutions in 1 country.
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Abstract
backgroundThe contribution of autophagy to cancer therapy resistance remains complex, mainly owing to the discrepancy of autophagy mechanisms in different therapy. However, the potential mechanisms of autophagy-mediated resistance to icotinib have yet to be elucidated.
methodsThe effect of autophagy in icotinib resistance was examined using a series of in vitro and in vivo assays. The results above were further verified in biopsy specimens of lung cancer patients before and after icotinib or gefitinib treatment.
resultsIcotinib increased ATG3, ATG5, and ATG7 expression, but without affecting Beclin-1, VPS34 and ATBG14 levels in icotinib-resistant lung cancer cells. Autophagy blockade by 3-MA or silencing Beclin-1 had no effects on resistance to icotinib. CQ effectively restored lung cancer cell sensitivity to icotinib in vitro and in vivo. Notably, aberrantly activated STAT3 and highly expressed FOXM1 were required for autophagy induced by icotinib, without the involvement of AMPK/mTOR pathway in this process. Alterations of STAT3 activity using genetic and/or pharmacological methods effectively affected FOXM1 and ATG7 levels increased by icotinib, with altering autophagy and icotinib-mediated apoptosis in resistant cells. Furthermore, silencing FOXM1 impaired up-regulated ATG7 induced by STAT3-CA and icotinib. STAT3/FOXM1 signalling blockade also reversed resistance to icotinib in vivo. Finally, we found a negative correlation between STAT3/FOXM1/ATG7 signalling activity and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment efficacy in patients undergoing EGFR-TKIs treatment.
conclusionsOur findings support that STAT3/FOXM1/ATG7 signalling-induced autophagy is a novel mechanism of resistance to icotinib, and provide insights into potential clinical values of ATG7-dependent autophagy in icotinib treatment.
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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.