1. Cytoneme-mediated signaling essential for tumorigenesis.
- Author
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Fereres, Sol, Hatori, Ryo, Hatori, Makiko, and Kornberg, Thomas B
- Subjects
Cell Membrane Structures ,Pseudopodia ,Animals ,Drosophila melanogaster ,Neoplasms ,Cell Transformation ,Neoplastic ,Neoplasm Metastasis ,Intercellular Signaling Peptides and Proteins ,Drosophila Proteins ,Receptors ,Invertebrate Peptide ,Models ,Animal ,Signal Transduction ,Tumor Microenvironment ,Imaginal Discs ,Carcinogenesis ,ErbB Receptors ,Wings ,Animal ,Cell Transformation ,Neoplastic ,Models ,Animal ,Receptors ,Invertebrate Peptide ,Wings ,Genetics ,Developmental Biology - Abstract
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.
- Published
- 2019