ArticleAutophagy2021
MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 220 citations in OpenAlex.
- Mechanistic insights into gallic acid-induced autophagy in triple negative breast cancer through network pharmacology, molecular docking, and in vitro validation.Functional & integrative genomics · 2026Article
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- Decoding Mitophagy in Breast Cancer: Biological Mechanisms, Dual Roles, and Clinical Implications.Cells · 2026Review
- Proton Radiation-Induced Cognitive Impairment via Disruption of Hippocampal Neuronal Mitophagic Homeostasis.Biomolecules · 2026Article
- Genome-wide association study identifies toll-like receptor four protein-mediated metabolic remodelling affecting gout pathogenesis.Journal of global health · 2026Observational
- Integrated computational and in vitro investigation to explore the preliminary anti-proliferative and anti-mitotic potential of γ-oryzanol against breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mitochondrial quality control in health and disease: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Tomatidine modulatesfibrosis-related markers by promoting autophagy in hepatic stellate cells via the ERK/MAPK-mTOR-ULK1 signaling pathway.Scientific reports · 2026Article
- Sirt3 Genetically Engineered Apoptotic Bodies Alleviate Skeletal Aging by Limiting Aggravated NLRP3 Inflammasome Activation of Senescent Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Targeting PTDSS1 to modulate GSH synthesis triggers mitophagy and induces ferroptosis in esophageal squamous cell carcinoma cells.Cell death & disease · 2026Article
- CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Mitophagy in bladder cancer: a double-edged sword in tumor progression and therapy.Journal of translational medicine · 2026Review
- ULK1 promotes metastatic progression in experimental models of epithelial ovarian cancer.Oncogene · 2026Article
- Targeting ULK1 and USP20 to modulate autophagy and chemosensitivity in cancer cell lines.Biomedical reports · 2026Article
- Stigmasterol reverses rituximab resistance in diffuse large B-cell lymphoma via the MAPK1 signaling pathway.Translational cancer research · 2026Article
- Malic enzyme 2 suppresses PINK1-Parkin-mediated mitophagy by stabilizing ATAD3A via competitive interaction with TRIM25.Cell death & disease · 2026Article
- NPC2 suppresses osteolytic metastasis in lung adenocarcinoma via the AKT/mTOR pathway and tumor-osteoclast crosstalk.iScience · 2026Article
- O-GlcNAcylation of IGF2BP2 promotes angiogenesis after ischemic stroke by stabilizing PPP2CA in an m6A-dependent manner : O-GlcNAcylation of IGF2BP2 alleviates ischemic brain injury.Journal of translational medicine · 2026Article
- Crosstalk between mitophagy and breast cancer: mechanisms of action and clinical applications.Journal of cancer research and clinical oncology · 2026Review
89 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of mitophagy in cancer is controversial. ULK1 is critical for induction of macroautophagy/autophagy and has a more specific role in mitophagy in response to hypoxia. Here, we show that ULK1 deficiency induces an invasive phenotype of breast cancer cells under hypoxia and increases osteolytic bone metastasis. Mechanistically, ULK1 depletion attenuates mitophagy ability during hypoxia. As a result, the accumulation of damaged, ROS-generating mitochondria leads to activation of the NLRP3 inflammasome, which induces abnormal soluble cytokines secretion, then promotes the differentiation and maturation of osteoclasts, and ultimately results in bone metastasis. Notably, phosphorylation of ULK1 by MAPK1/ERK2-MAPK3/ERK1 kinase triggers its interaction with BTRC and subsequent K48-linked ubiquitination and proteasome degradation. Also, a clearly negative correlation between the expression levels of ULK1 and p-MAPK1/3 was observed in human breast cancer tissues. The MAP2K/MEK inhibitor trametinib is sufficient to restore mitophagy function via upregulation of ULK1, leading to inhibition of NLRP3 inflammasome activation, thereby reduces bone metastasis. These results indicate that
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