Cytoneme-mediated signaling essential for tumorigenesis.
In: PLoS genetics, Jg. 15 (2019-09-30), Heft 9
Online
academicJournal
- e1008415
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.
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Cytoneme-mediated signaling essential for tumorigenesis.
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Autor/in / Beteiligte Person: | Fereres, Sol ; Hatori, Ryo ; Hatori, Makiko ; Kornberg, Thomas B |
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Zeitschrift: | PLoS genetics, Jg. 15 (2019-09-30), Heft 9 |
Veröffentlichung: | eScholarship, University of California, 2019 |
Medientyp: | academicJournal |
Umfang: | e1008415 |
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