Your browser doesn't support javascript.
loading
An In Vivo CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression.
Scheidmann, Manuel C; Castro-Giner, Francesc; Strittmatter, Karin; Krol, Ilona; Paasinen-Sohns, Aino; Scherrer, Ramona; Donato, Cinzia; Gkountela, Sofia; Szczerba, Barbara M; Diamantopoulou, Zoi; Muenst, Simone; Vlajnic, Tatjana; Kunz, Leo; Vetter, Marcus; Rochlitz, Christoph; Taylor, Verdon; Giachino, Claudio; Schroeder, Timm; Platt, Randall J; Aceto, Nicola.
Afiliación
  • Scheidmann MC; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Castro-Giner F; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Strittmatter K; Department of Biology, Molecular Oncology Laboratory, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
  • Krol I; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
  • Paasinen-Sohns A; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Scherrer R; Department of Biology, Molecular Oncology Laboratory, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
  • Donato C; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Gkountela S; Department of Biology, Molecular Oncology Laboratory, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
  • Szczerba BM; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Diamantopoulou Z; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Muenst S; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Vlajnic T; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Kunz L; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Vetter M; Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, Basel, Switzerland.
  • Rochlitz C; Department of Biology, Molecular Oncology Laboratory, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
  • Taylor V; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Giachino C; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Schroeder T; Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
  • Platt RJ; Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
  • Aceto N; Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Cancer Res ; 82(4): 681-694, 2022 02 15.
Article en En | MEDLINE | ID: mdl-34916221
Blood-borne metastasis of breast cancer involves a series of tightly regulated sequential steps, including the growth of a primary tumor lesion, intravasation of circulating tumor cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each of these steps are poorly understood in physiologically relevant contexts, owing to the rarity of experimental models that faithfully recapitulate the biology, growth kinetics, and tropism of human breast cancer. Here, we conducted an in vivo loss-of-function CRISPR screen in newly derived CTC xenografts, unique in their ability to spontaneously mirror the human disease, and identified specific genetic dependencies for each step of the metastatic process. Validation experiments revealed sensitivities to inhibitors that are already available, such as PLK1 inhibitors, to prevent CTC intravasation. Together, these findings present a new tool to reclassify driver genes involved in the spread of human cancer, providing insights into the biology of metastasis and paving the way to test targeted treatment approaches. SIGNIFICANCE: A loss-of-function CRISPR screen in human CTC-derived xenografts identifies genes critical for individual steps of the metastatic cascade, suggesting novel drivers and treatment opportunities for metastatic breast cancers.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Biomarcadores de Tumor / Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas / Células Neoplásicas Circulantes Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Res Año: 2022 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Biomarcadores de Tumor / Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas / Células Neoplásicas Circulantes Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Cancer Res Año: 2022 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos