ArticleCancer biology & therapy2019
GATA6-upregulating autophagy promotes TKI resistance in nonsmall cell lung cancer.
Article in Cancer biology & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Repurposing dihydroartemisinin as a novel anticancer agent against colorectal cancer stem cells.Journal of food and drug analysis · 2025Article
- Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer.Antioxidants (Basel, Switzerland) · 2024Article
- Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.World journal of gastroenterology · 2024Article
- GATA6 inhibits the biological function of non-small cell lung cancer by modulating glucose metabolism.Journal of cancer research and clinical oncology · 2024Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- The Molecular Landscape of Pancreatobiliary Cancers for Novel Targeted Therapies From Real-World Genomic Profiling.Journal of the National Cancer Institute · 2022Article
- Identifying General Tumor and Specific Lung Cancer Biomarkers by Transcriptomic Analysis.Biology · 2022Article
- ATF4-mediated microRNA-145/HDAC4/p53 axis affects resistance of colorectal cancer cells to 5-fluorouracil by regulating autophagy.Cancer chemotherapy and pharmacology · 2022Article
- Dual Roles of Lactate in EGFR-TKI-Resistant Lung Cancer by Targeting GPR81 and MCT1.Journal of oncology · 2022Article
- Unfolding the role of autophagy in the cancer metabolism.Biochemistry and biophysics reports · 2021Article
- PKCδ-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs.Oncogene · 2021Article
- GATA binding protein 6 (GATA6) is co-amplified with PIK3CA in patients with esophageal adenocarcinoma and is linked to neoadjuvant therapy.Journal of cancer research and clinical oncology · 2021Article
- EmergingGenes · 2020Review
- Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot.Biology · 2020Article
- GATA6 Exerts Potent Lung Cancer Suppressive Function by Inducing Cell Senescence.Frontiers in oncology · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy plays a complicated role in tumorigenesis, and the effects of autophagy in drug resistance have not been fully known. The aim of this study was to evaluate autophagy activity in lung cancer cells derived from different origins and explore the mechanism regulating autophagy in tyrosine kinase inhibitor (TKI) resistance. We found basal level of autophagy had no significant increase in resistant H1650 and H1975 cells compared with sensitive HCC827 and PC9 cells. After erlotinib treatment, the autophagy activity enhanced threefold in H1650 cells but a little in H1975 cells. Inhibiting autophagy with 3-MA increased apoptosis in H1650 rather than H1975 cells. Combined with transmission microscope, results showed PC9 cells tended to be apoptotic and more autophagosomes formed in H1650 cells, which may be correlated with cell viability. GATA6 expression was found markedly elevated in H1650 cells after erlotinib and knocking down GATA6 led to significantly reduced autophagy activity and cell viability. Furthermore, a significant increase of GATA6 and LC3-II expression was observed in insensitive tissues compared with sensitive ones by immunostaining in nonsmall cell lung cancer (NSCLC) patients. With chi-square test, we found GATA6 was positively correlated with LC3-II. The Kaplan-Meier curve analyses further showed patients with high GATA6 had lower overall survival and progression-free survival rates than those with low GATA6 after EGFR-TKI treatment. Our results suggest that GATA6 could enhance autophagy activity contributing to TKI resistance. Targeting GATA6 and autophagy together with TKI may be promising to overcome drug resistance in NSCLC.
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