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Cytoneme-mediated signaling essential for tumorigenesis.
Fereres, Sol; Hatori, Ryo; Hatori, Makiko; Kornberg, Thomas B.
Afiliação
  • Fereres S; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, United States of America.
  • Hatori R; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, United States of America.
  • Hatori M; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, United States of America.
  • Kornberg TB; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, United States of America.
PLoS Genet ; 15(9): e1008415, 2019 09.
Article em En | MEDLINE | ID: mdl-31568500
Communication between neoplastic cells and cells of their microenvironment is critical to cancer progression. To investigate the role of cytoneme-mediated signaling as a mechanism for distributing growth factor signaling proteins between tumor and tumor-associated cells, we analyzed EGFR and RET Drosophila tumor models and tested several genetic loss-of-function conditions that impair cytoneme-mediated signaling. Neuroglian, capricious, Irk2, SCAR, and diaphanous are genes that cytonemes require during normal development. Neuroglian and Capricious are cell adhesion proteins, Irk2 is a potassium channel, and SCAR and Diaphanous are actin-binding proteins, and the only process to which they are known to contribute jointly is cytoneme-mediated signaling. We observed that diminished function of any one of these genes suppressed tumor growth and increased organism survival. We also noted that EGFR-expressing tumor discs have abnormally extensive tracheation (respiratory tubes) and ectopically express Branchless (Bnl, a FGF) and FGFR. Bnl is a known inducer of tracheation that signals by a cytoneme-mediated process in other contexts, and we determined that exogenous over-expression of dominant negative FGFR suppressed tumor growth. Our results are consistent with the idea that cytonemes move signaling proteins between tumor and stromal cells and that cytoneme-mediated signaling is required for tumor growth and malignancy.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pseudópodes / Transformação Celular Neoplásica / Carcinogênese Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pseudópodes / Transformação Celular Neoplásica / Carcinogênese Idioma: En Ano de publicação: 2019 Tipo de documento: Article