Your browser doesn't support javascript.
loading
Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.
Floerchinger, Alessia; Murphy, Kendelle J; Latham, Sharissa L; Warren, Sean C; McCulloch, Andrew T; Lee, Young-Kyung; Stoehr, Janett; Mélénec, Pauline; Guaman, Cris S; Metcalf, Xanthe L; Lee, Victoria; Zaratzian, Anaiis; Da Silva, Andrew; Tayao, Michael; Rolo, Sonia; Phimmachanh, Monica; Sultani, Ghazal; McDonald, Laura; Mason, Susan M; Ferrari, Nicola; Ooms, Lisa M; Johnsson, Anna-Karin E; Spence, Heather J; Olson, Michael F; Machesky, Laura M; Sansom, Owen J; Morton, Jennifer P; Mitchell, Christina A; Samuel, Michael S; Croucher, David R; Welch, Heidi C E; Blyth, Karen; Caldon, C Elizabeth; Herrmann, David; Anderson, Kurt I; Timpson, Paul; Nobis, Max.
Afiliação
  • Floerchinger A; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Murphy KJ; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Latham SL; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Warren SC; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • McCulloch AT; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Lee YK; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Stoehr J; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Mélénec P; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Guaman CS; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Metcalf XL; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Lee V; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Zaratzian A; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Da Silva A; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Tayao M; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Rolo S; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK.
  • Phimmachanh M; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Sultani G; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • McDonald L; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK.
  • Mason SM; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK.
  • Ferrari N; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK; Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G111QH, UK.
  • Ooms LM; Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, VIC 3800, Australia.
  • Johnsson AE; Signalling Programme, Babraham Institute, Cambridge CB223AT, UK.
  • Spence HJ; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Olson MF; Department of Chemistry and Biology, Ryerson University, Toronto ON, M5B 2K3, Canada.
  • Machesky LM; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Sansom OJ; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK; Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G111QH, UK.
  • Morton JP; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK; Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G111QH, UK.
  • Mitchell CA; Cancer Program, Monash Biomedicine Discovery Institute, and Department of Biochemistry and Molecular Biology, Monash University, VIC 3800, Australia.
  • Samuel MS; Centre for Cancer Biology, SA Pathology and University of South Australia; and the School of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
  • Croucher DR; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Welch HCE; Signalling Programme, Babraham Institute, Cambridge CB223AT, UK.
  • Blyth K; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK; Institute of Cancer Sciences, University of Glasgow, Switchback Road, Glasgow G111QH, UK.
  • Caldon CE; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Herrmann D; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
  • Anderson KI; Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G611BD, UK; Francis Crick Institute, London NW11AT, UK.
  • Timpson P; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia. Electronic address: p.timpson@garvan.org.au.
  • Nobis M; The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia. Electronic address: m.nobis@garvan.org.au.
Cell Rep ; 36(11): 109689, 2021 09 14.
Article em En | MEDLINE | ID: mdl-34525350
ABSTRACT
Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Técnicas Biossensoriais / Proteínas rac1 de Ligação ao GTP Tipo de estudo: Guideline Limite: Animals / Female / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Técnicas Biossensoriais / Proteínas rac1 de Ligação ao GTP Tipo de estudo: Guideline Limite: Animals / Female / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Austrália