ArticleAutophagy2013
IκB kinase complex (IKK) triggers detachment-induced autophagy in mammary epithelial cells independently of the PI3K-AKT-MTORC1 pathway.
Article in Autophagy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 72 citations in OpenAlex.
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- The potential role of hydrogen sulfide-autophagy axis in diseases.Journal of physiology and biochemistry · 2025Review
- Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma.Discover oncology · 2025Article
- Loss of DDX24 inhibits lung cancer progression by stimulating IKBKG splicing-mediated autophagy.Theranostics · 2025Article
- Acod1 expression in cancer cells promotes immune evasion through the generation of inhibitory peptides.Cell reports · 2024Article
- Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- Levistolide a Attenuates Acute Kidney Injury in Mice by Inhibiting the TLR-4/NF-κB Pathway.Drug design, development and therapy · 2024Article
- The Crosstalk between Autophagy and Nrf2 Signaling in Cancer: from Biology to Clinical Applications.International journal of biological sciences · 2024Review
- Integrin-associated transcriptional characteristics of circulating tumor cells in breast cancer patients.PeerJ · 2024Article
- THUMPD3 regulates alternative splicing of ECM transcripts in human lung cancer cells and promotes proliferation and migration.PloS one · 2024Article
- The Prognosis of Cancer Depends on the Interplay of Autophagy, Apoptosis, and Anoikis within the Tumor Microenvironment.Cell biochemistry and biophysics · 2023Review
- Recent Advances in the Role of Autophagy in Endocrine-Dependent Tumors.Endocrine reviews · 2023Review
- Impact of context-dependent autophagy states on tumor progression.Nature cancer · 2023Review
- Exercise-activated hepatic autophagy via the FN1-α5β1 integrin pathway drives metabolic benefits of exercise.Cell metabolism · 2023Article
- The Role of Autophagy in Breast Cancer Metastasis.Biomedicines · 2023Review
- Protective Effects of NaHS/miR-133a-3p on Lipopolysaccharide-Induced Cardiomyocytes Injury.Journal of toxicology · 2023Article
- Swine acute diarrhea syndrome coronavirus induces autophagy to promote its replication via the Akt/mTOR pathway.iScience · 2022Article
- Article
- Identification of an autophagy-related gene signature for predicting prognosis and immune activity in pancreatic adenocarcinoma.Scientific reports · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Adherent cells require proper integrin-mediated extracellular matrix (ECM) engagement for growth and survival; normal cells deprived of proper ECM contact undergo anoikis. At the same time, autophagy is induced as a survival pathway in both fibroblasts and epithelial cells upon ECM detachment. Here, we further define the intracellular signals that mediate detachment-induced autophagy and uncover an important role for the IκB kinase (IKK) complex in the induction of autophagy in mammary epithelial cells (MECs) deprived of ECM contact. Whereas the PI3K-AKT-MTORC1 pathway activation potently inhibits autophagy in ECM-detached fibroblasts, enforced activation of this pathway is not sufficient to suppress detachment-induced autophagy in MECs. Instead, inhibition of IKK, as well as its upstream regulator, MAP3K7/TAK1, significantly attenuates detachment-induced autophagy in MECs. Furthermore, function-blocking experiments corroborate that both IKK activation and autophagy induction result from decreased ITGA3-ITGB1 (α3β1 integrin) function. Finally, we demonstrate that pharmacological IKK inhibition enhances anoikis and accelerates luminal apoptosis during acinar morphogenesis in three-dimensional culture. Based on these results, we propose that the IKK complex functions as a key mediator of detachment-induced autophagy and anoikis resistance in epithelial cells.
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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.