ArticleThe Journal of cell biology2014
p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion.
Article in The Journal of cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Context-dependent roles of HtrA2/Omi in ovarian cancer: mitochondrial apoptotic function linking platinum sensitivity and acquired chemoresistance-a narrative review.Translational cancer research · 2026Review
- RING finger E3 ubiquitin ligases: novel therapeutic opportunities in melanoma.Cellular & molecular biology letters · 2026Review
- The tumor suppressor LACTB remodels mitochondria to promote cytochrome c release and apoptosis.Science advances · 2025Article
- Identification and validation of autophagy-related genes in sepsis based on bioinformatics studies.Virology journal · 2025Article
- Mitochondrial fatty acid oxidation drives senescence.Science advances · 2024Article
- Loss of p53 function promotes DNA damage-induced formation of nuclear actin filaments.Cell death & disease · 2023Article
- A new function for the serine protease HtrA2 in controlling radiation-induced senescence in cancer cells.Molecular oncology · 2022Article
- Noxa and Puma genes regulated by hTERT promoter can mitigate growth and induce apoptosis in hepatocellular carcinoma mouse model.Journal of Cancer · 2022Article
- Mutant TP53 interacts with BCAR1 to contribute to cancer cell invasion.British journal of cancer · 2021Article
- Antiproliferative chromone derivatives induce K562 cell death through endogenous and exogenous pathways.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- STAT3 Localizes in Mitochondria-Associated ER Membranes Instead of in Mitochondria.Frontiers in cell and developmental biology · 2020Article
- Depletion of mitochondrial protease OMA1 alters proliferative properties and promotes metastatic growth of breast cancer cells.Scientific reports · 2019Article
- Role of ALDH1A1 and HTRA2 expression in CCL2/CCR2-mediated breast cancer cell growth and invasion.Biology open · 2019Article
- Mitochondrial protein E2F3d, a distinctive E2F3 product, mediates hypoxia-induced mitophagy in cancer cells.Communications biology · 2019Article
- LonP1 Differently Modulates Mitochondrial Function and Bioenergetics of Primary Versus Metastatic Colon Cancer Cells.Frontiers in oncology · 2018Article
- Ovarian serous carcinomas acquire cisplatin resistance and increased invasion through downregulation of the high-temperature-required protein A2 (HtrA2), following repeated treatment with cisplatin.Medical oncology (Northwood, London, England) · 2017Article
- Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction.Scientific reports · 2016Article
- Cloning and Transcriptional Activity of the Mouse Omi/HtrA2 Gene Promoter.International journal of molecular sciences · 2016Article
- Functions of the Tumor Suppressors p53 and Rb in Actin Cytoskeleton Remodeling.BioMed research international · 2016Review
- p53 regulates cytoskeleton remodeling to suppress tumor progression.Cellular and molecular life sciences : CMLS · 2015Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Ras-driven invasion. However, its mechanism remains poorly understood. Here we show that p53 induces activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton. Oncogenic Ras increases accumulation of p53 in the cytoplasm, which promotes the translocation of p38 mitogen-activated protein kinase (MAPK) into mitochondria and induces phosphorylation of HtrA2/Omi. Concurrently, oncogenic Ras also induces mitochondrial fragmentation, irrespective of p53 expression, causing the release of HtrA2/Omi from mitochondria into the cytosol. Phosphorylated HtrA2/Omi therefore cleaves β-actin and decreases the amount of filamentous actin (F-actin) in the cytosol. This ultimately down-regulates p130 Crk-associated substrate (p130Cas)-mediated lamellipodia formation, countering the invasive phenotype initiated by oncogenic Ras. Our novel findings provide insights into the mechanism by which p53 prevents the malignant progression of transformed 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.