ArticleMolecular cancer2015
Convergence of eicosanoid and integrin biology: 12-lipoxygenase seeks a partner.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- MAGL Inhibition Relieves Psoriasiform Inflammation and Pruritus Via Modulation of ALOX12-12-HETE Axis in Mice.Inflammation · 2026Article
- Inhibition of PGK1 ameliorates acute kidney injury through inactivating the PKM2/ALOX12/ferroptosis pathway in a study with male mice.Nature communications · 2025Article
- Human Umbilical Cord Mesenchymal Stem Cell Exosome-derived miR-335-5p Alleviated Lipopolysaccharide-induced Acute Lung Injury by Regulating the m6A Level of ITGβ4 Gene.Current medicinal chemistry · 2024Article
- Newly identified form of phenotypic plasticity of cancer: immunogenic mimicry.Cancer metastasis reviews · 2023Review
- Establishment of a novel prognostic prediction model through bioinformatics analysis for prostate cancer based on ferroptosis-related genes and its application in immune cell infiltration.Translational andrology and urology · 2022Article
- Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker.Biomolecules · 2021Review
- RAD001 targeted HUVECs reverses 12-lipoxygenase-induced angiogenesis in oesophageal squamous cell carcinoma.Journal of cellular and molecular medicine · 2021Article
- Platelets in aging and cancer-"double-edged sword".Cancer metastasis reviews · 2020Review
- Evidence that ABC transporter-mediated autocrine export of an eicosanoid signaling molecule enhances germ cell chemotaxis in the colonial tunicateDevelopment (Cambridge, England) · 2020Article
- 12-Lipoxygenase promotes epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway in gastric cancer cells.OncoTargets and therapy · 2019Article
- An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury.Nature medicine · 2018Article
- β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.Investigative ophthalmology & visual science · 2017Article
- Convergence of eicosanoid and integrin biology: Role of Src in 12-LOX activation.Experimental cell research · 2017Article
- 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Platelet-12 lipoxygenase targeting via a newly synthesized curcumin derivative radiolabeled with technetium-99m.Chemistry Central journal · 2016Article
- Protease-activated receptors (PARs)--biology and role in cancer invasion and metastasis.Cancer metastasis reviews · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundIntegrins and enzymes of the eicosanoid pathway are both well-established contributors to cancer. However, this is the first report of the interdependence of the two signaling systems. In a screen for proteins that interacted with, and thereby potentially regulated, the human platelet-type 12-lipoxygenase (12-LOX, ALOX12), we identified the integrin β4 (ITGB4).
methodsUsing a cultured mammalian cell model, we have demonstrated that ITGB4 stimulation leads to recruitment of 12-LOX from the cytosol to the membrane where it physically interacts with the integrin to become enzymatically active to produce 12(S)-HETE, a known bioactive lipid metabolite that regulates numerous cancer phenotypes.
resultsThe net effect of the interaction was the prevention of cell death in response to starvation. Additionally, regulation of β4-mediated, EGF-stimulated invasion was shown to be dependent on 12-LOX, and downstream Erk signaling in response to ITGB4 activation also required 12-LOX.
conclusionsThis is the first report of an enzyme of the eicosanoid pathway being recruited to and regulated by activated β4 integrin. Integrin β4 has recently been shown to induce expansion of prostate tumor progenitors and there is a strong correlation between stage/grade of prostate cancer and 12-LOX expression. The 12-LOX enzymatic product, 12(S)-HETE, regulates angiogenesis and cell migration in many cancer types. Therefore, disruption of integrin β4-12LOX interaction could reduce the pro-inflammatory oncogenic activity of 12-LOX. This report on the consequences of 12-LOX and ITGB4 interaction sets a precedent for the linkage of integrin and eicosanoid biology through direct protein-protein association.
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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.