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A Lung Organotypic Coculture Reveals a Role for TFEB-Lysosomal Axis in the Survival of Disseminated Dormant Cancer Cells.
Zangrossi, Manuela; Chakravarty, Probir; Romani, Patrizia; Dupont, Sirio; Hooper, Steven; Sahai, Erik; Montagner, Marco.
Afiliación
  • Zangrossi M; Department of Molecular Medicine, University of Padua, Viale G. Colombo, 3, 35126 Padua, Italy.
  • Chakravarty P; Bioinformatics Platform, Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Romani P; Department of Molecular Medicine, University of Padua, Viale G. Colombo, 3, 35126 Padua, Italy.
  • Dupont S; Department of Molecular Medicine, University of Padua, Viale G. Colombo, 3, 35126 Padua, Italy.
  • Hooper S; Tumor Cell Biology Lab., Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Sahai E; Tumor Cell Biology Lab., Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • Montagner M; Department of Molecular Medicine, University of Padua, Viale G. Colombo, 3, 35126 Padua, Italy.
Cancers (Basel) ; 13(5)2021 Feb 28.
Article en En | MEDLINE | ID: mdl-33670926
(1) Background: metastatic relapse following a prolonged period of disease-free survival is a common cause of mortality for many cancer patients. Disseminated dormant cancer cells (DDCCs) lie below the radar before waking up years, or even decades, after the removal of the primary tumor. This implies that they are able to survive in a latent state in a foreign environment for an extended period of time supported by intrinsic and extrinsic factors still to be elucidated. (2) Methods: we employed a coculture of DDCCs with lung epithelial cells together with RNA sequencing analysis to understand the overlap in gene transcription between in vivo and cocultured DDCCs. (3) Results: we found a significant overlap between the processes activated in DDCCs from lungs and in the coculture, as well as in alveolar type I cells in vivo and in coculture. We identified the transcription factor EB (TFEB)-lysosomal axis as a relevant process activated in DDCCs upon dissemination to the lung and confirmed the results in our lung coculture. Interestingly, breast cancer patients with a higher expression of TFEB targets show increased likelihood of developing relapses. (4) Conclusions: we propose that lysosomal accumulation following TFEB activation is an important feature of breast cancer DDCCs that might be exploited for future therapeutic interventions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Cancers (Basel) Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza