Background: Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown.
Methods: We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo.
Results: We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness.
Conclusions: Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC.
{"title":"Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth.","authors":"Margherita Zamberlan, Amandine Boeckx, Florian Muller, Federica Vinelli, Olivier Ek, Caterina Vianello, Emeline Coart, Keitaro Shibata, Aurélie Christian, Francesca Grespi, Marta Giacomello, Ingrid Struman, Luca Scorrano, Stéphanie Herkenne","doi":"10.1186/s13046-022-02304-6","DOIUrl":"10.1186/s13046-022-02304-6","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial fusion and fission proteins have been nominated as druggable targets in cancer. Whether their inhibition is efficacious in triple negative breast cancer (TNBC) that almost invariably develops chemoresistance is unknown.</p><p><strong>Methods: </strong>We used a combination of bioinformatics analyses of cancer genomic databases, genetic and pharmacological Optic Atrophy 1 (OPA1) inhibition, mitochondrial function and morphology measurements, micro-RNA (miRNA) profiling and formal epistatic analyses to address the role of OPA1 in TNBC proliferation, migration, and invasion in vitro and in vivo.</p><p><strong>Results: </strong>We identified a signature of OPA1 upregulation in breast cancer that correlates with worse prognosis. Accordingly, OPA1 inhibition could reduce breast cancer cells proliferation, migration, and invasion in vitro and in vivo. Mechanistically, while OPA1 silencing did not reduce mitochondrial respiration, it increased levels of miRNAs of the 148/152 family known to inhibit tumor growth and invasiveness. Indeed, these miRNAs were epistatic to OPA1 in the regulation of TNBC cells growth and invasiveness.</p><p><strong>Conclusions: </strong>Our data show that targeted inhibition of the mitochondrial fusion protein OPA1 curtails TNBC growth and nominate OPA1 as a druggable target in TNBC.</p>","PeriodicalId":79969,"journal":{"name":"Hospital aviation","volume":"5 1","pages":"95"},"PeriodicalIF":11.4,"publicationDate":"2022-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78131704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1989-09-01DOI: 10.1016/S0740-8315(89)80063-4
{"title":"AStar crash in Washington fatal to four","authors":"","doi":"10.1016/S0740-8315(89)80063-4","DOIUrl":"https://doi.org/10.1016/S0740-8315(89)80063-4","url":null,"abstract":"","PeriodicalId":79969,"journal":{"name":"Hospital aviation","volume":"8 9","pages":"Pages 22-23"},"PeriodicalIF":0.0,"publicationDate":"1989-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0740-8315(89)80063-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137256156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1989-09-01DOI: 10.1016/S0740-8315(89)80062-2
{"title":"King Air crash in Oregon fatal for three","authors":"","doi":"10.1016/S0740-8315(89)80062-2","DOIUrl":"https://doi.org/10.1016/S0740-8315(89)80062-2","url":null,"abstract":"","PeriodicalId":79969,"journal":{"name":"Hospital aviation","volume":"8 9","pages":"Page 22"},"PeriodicalIF":0.0,"publicationDate":"1989-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0740-8315(89)80062-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137256157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1989-09-01DOI: 10.1016/S0740-8315(89)80058-0
MD, FACEP B.J. Ringenberg , MD D. Wysham , MD, FACC C.W. White , MS K.R. Stults , MD, FACC M.A. Kienzle
Patients receiving intravenous streptokinase (IV-STK) during acute myocardial infarction (AMI) may be at risk for arrhythmias complicating aeromedical transportation to a tertiary care center.
A brief report of forty adult patients prospectively studied during helicopter transport utilizing continuous ambulatory electrocardiography (Holter monitor) to determine the incidence and severity of cardiac arrhythmias is presented. Patients with AMI treated with IV-STK were compared to patients with a variety of other cardiac and non-cardiac conditions transported by air. Although high grade ventricular arrhythmias were more common in the patients receiving IV-STK, no patient experienced symptomatic arrhythmias requiring defibrillation or cardioversion. The arrhythmias recorded did not correlate with clinical reperfusion of the infarct related vessel. We conclude that aeromedical transport of patients with AMI treated with IV-STK can be accomplished safely.
{"title":"Incidence of arrhythmias during air transportation following intravenous streptokinase therapy","authors":"MD, FACEP B.J. Ringenberg , MD D. Wysham , MD, FACC C.W. White , MS K.R. Stults , MD, FACC M.A. Kienzle","doi":"10.1016/S0740-8315(89)80058-0","DOIUrl":"10.1016/S0740-8315(89)80058-0","url":null,"abstract":"<div><p>Patients receiving intravenous streptokinase (IV-STK) during acute myocardial infarction (AMI) may be at risk for arrhythmias complicating aeromedical transportation to a tertiary care center.</p><p>A brief report of forty adult patients prospectively studied during helicopter transport utilizing continuous ambulatory electrocardiography (Holter monitor) to determine the incidence and severity of cardiac arrhythmias is presented. Patients with AMI treated with IV-STK were compared to patients with a variety of other cardiac and non-cardiac conditions transported by air. Although high grade ventricular arrhythmias were more common in the patients receiving IV-STK, no patient experienced symptomatic arrhythmias requiring defibrillation or cardioversion. The arrhythmias recorded did not correlate with clinical reperfusion of the infarct related vessel. We conclude that aeromedical transport of patients with AMI treated with IV-STK can be accomplished safely.</p></div>","PeriodicalId":79969,"journal":{"name":"Hospital aviation","volume":"8 9","pages":"Pages 6-10"},"PeriodicalIF":0.0,"publicationDate":"1989-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0740-8315(89)80058-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56182239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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