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: 10.1371/journal.pgen.1008415


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


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