Cytoneme-mediated signaling essential for tumorigenesis
Sol Fereres1, Ryo Hatori1, Makiko Hatori1
1Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, United States of America.
Plos Genetics
|October 1, 2019
Summary
Cytonemes, cellular nanotubes, distribute growth factors crucial for tumor progression. Inhibiting cytoneme-mediated signaling in Drosophila tumor models suppressed growth and improved survival, highlighting their role in cancer malignancy.
Area of Science:
- Cell Biology
- Cancer Research
- Developmental Biology
Background:
- Intercellular communication between neoplastic and microenvironment cells is vital for cancer progression.
- Cytonemes, cellular extensions, are implicated in distributing signaling molecules.
- Understanding cytoneme-mediated signaling in cancer is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of cytoneme-mediated signaling in distributing growth factor signaling proteins.
- To analyze the impact of impaired cytoneme function on tumor growth and malignancy in Drosophila models.
- To identify key genes involved in cytoneme-mediated signaling essential for tumor progression.
Main Methods:
- Utilized Drosophila tumor models expressing Epidermal Growth Factor Receptor (EGFR) and RET.
- Tested genetic loss-of-function conditions for genes essential for cytoneme formation and function (Neuroglian, capricious, Irk2, SCAR, diaphanous).
- Analyzed tumor growth, organism survival, tracheation patterns, and gene expression (Branchless, FGFR).
Main Results:
- Diminished function of Neuroglian, capricious, Irk2, SCAR, or diaphanous suppressed tumor growth and increased organism survival.
- EGFR-expressing tumors showed increased tracheation and ectopic expression of Branchless (Bnl) and Fibroblast Growth Factor Receptor (FGFR).
- Over-expression of dominant-negative FGFR suppressed tumor growth, confirming Bnl/FGFR signaling's role.
Conclusions:
- Cytonemes actively transport signaling proteins between tumor and stromal cells.
- Cytoneme-mediated signaling is essential for tumor growth and malignancy.
- Targeting cytoneme function presents a potential therapeutic strategy for cancer.
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