Cytoneme-mediated signaling essential for tumorigenesis
Autoři:
Sol Fereres aff001; Ryo Hatori aff001; Makiko Hatori aff001; Thomas B. Kornberg aff001
Působiště autorů:
Cardiovascular Research Institute, University of California, San Francisco, California, United States of America
aff001
Vyšlo v časopise:
Cytoneme-mediated signaling essential for tumorigenesis. PLoS Genet 15(9): e32767. doi:10.1371/journal.pgen.1008415
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008415
Souhrn
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 and 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.
Klíčová slova:
Carcinogenesis – Drosophila melanogaster – Epithelial cells – Larvae – Myoblasts – DPP signaling cascade – Paracrine signaling – Stromal cells
Zdroje
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Štítky
Genetika Reprodukční medicínaČlánek vyšel v časopise
PLOS Genetics
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