ArticleAutophagy2019
Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 133 citations in OpenAlex.
- GATA6-CRT axis promotes stress-associated autophagy, EMT, and stemness-associated traits in pancreatic cancer.Cell death & disease · 2026Article
- Autophagy as a Redox Rheostat Linking Cigarette Smoke, Electronic Cigarettes, and Nicotine Exposure to Lung Development, Disease, and Interorgan Communication.Comprehensive physiology · 2026Review
- Allicin inhibits colon cancer cells biological activity by regulating lncRNA UCA1 via autophagy stimulating.Discover oncology · 2026Article
- Role of autophagy in tumorigenesis and drug resistance: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- A review of autophagy in the pancreas: normal physiology and pathophysiology.Autophagy reports · 2026Review
- Circ_0000972 Inhibits Hepatocellular Carcinoma Cell Stemness by Targeting miR-96-5p/PFN1.Biochemical genetics · 2025Article
- Oncogenic RAS induces a distinctive form of non-canonical autophagy mediated by the P38-ULK1-PI4KB axis.Cell research · 2025Article
- KAT2B inhibits proliferation and invasion via inactivating TGF-β/Smad3 pathway-medicated autophagy and EMT in epithelial ovarian cancer.Scientific reports · 2025Article
- Autophagy in the lung: guardian of homeostasis or driver of disease.Autophagy reports · 2025Review
- IKBKE modulates autophagy and progestin resistance in endometrial cancer.Frontiers in oncology · 2025Article
- SQSTM1/p62 Mediates the Effects of CPNE3 on the Epithelialmesenchymal Transition and Migration Inhibition of Lung Adenocarcinoma Cells.Current medicinal chemistry · 2025Article
- MiR-125b-5p alleviates pulmonary fibrosis by inhibiting TGFβ1-mediated epithelial-mesenchymal transition via targeting BAK1.Respiratory research · 2024Article
- LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis.Genes & diseases · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- CCL2 promotes metastasis and epithelial-mesenchymal transition of non-small cell lung cancer via PI3K/Akt/mTOR and autophagy pathways.Cell proliferation · 2024Article
- Dysregulated bidirectional epithelial-mesenchymal crosstalk: a core determinant of lung fibrosis progression.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Contribution of Autophagy to Epithelial Mesenchymal Transition Induction during Cancer Progression.Cancers · 2024Review
- SQSTM1/p62 promotes the progression of gastric cancer through epithelial-mesenchymal transition.Heliyon · 2024Article
- PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway.Journal of translational medicine · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Macroautophagy/autophagy inhibition is a novel anticancer therapeutic strategy, especially for tumors driven by mutant RAS. Here, we demonstrate that autophagy inhibition in RAS-mutated cells induces epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor invasion. This is at least partially achieved by triggering the NFKB/NF-κB pathway via SQSTM1/p62. Knockdown of ATG3 or ATG5 increases oncogenic RAS-induced expression of ZEB1 and SNAI2/Snail2, and activates NFKB activity. Depletion of SQSTM1 abolishes the activation of the NFKB pathway induced by autophagy inhibition in RAS-mutated cells. NFKB pathway inhibition by depletion of RELA/p65 blocks this EMT induction. Finally, accumulation of SQSTM1 protein correlates with loss of CDH1/E-cadherin expression in pancreatic adenocarcinoma. Together, we suggest that combining autophagy inhibition with NFKB inhibitors may therefore be necessary to treat RAS-mutated cancer. Abbreviations: 4-OHT: 4-hydroxytamoxifen; DIC: differential interference contrast; EMT: epithelial-mesenchymal transition; ESR: estrogen receptor; MAPK/ERK: mitogen-activated protein kinase; iBMK: immortalized baby mouse kidney epithelial cells; MET: mesenchymal-epithelial transition; PI3K: phosphoinositide 3-kinase; RNAi: RNA interference; TGFB/TGF-β: transforming growth factor beta; TNF: tumor necrosis factor; TRAF6: TNF receptor associated factor 6.
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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.