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The anticancer drug Gefitinib is a tyrosine kinase inhibitor with selectivity for the Epidermal Growth Factor Receptor (EGFR/ErbB1). As the C. elegans EGF receptor LET-23 shares notable structural homology over its kinase domain with human EGFR, we wished to examine whether Gefitinib treatment can interfere with LET-23-dependent processes. We show that Gefitinib disrupts C. elegans stress-induced sleep (SIS) but does not impact EGF overexpression-induced sleep nor vulva induction. These findings indicate that Gefitinib does not interfere with LET-23 signaling and impairs SIS through an off-target mechanism.
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This content will become publicly available on September 15, 2026
IGEG-2 is a C. elegans EGFR ligand
Across species, Epidermal Growth Factor (EGF) family ligands and their receptors participate in developmental and physiological cell-cell signaling events. C. elegans possesses a single EGF receptor, LET-23/EGFR, and two characterized EGF ligands. LIN-3/EGF is well-known for its role in vulval induction, and SISS-1/EGF mediates stress-induced sleep. The C. elegans genome harbors another predicted EGF family member, igeg-2, which has not been characterized. To determine if IGEG-2 is a functional EGFR ligand, we examined whether it can activate known LET-23-dependent processes. We found that ubiquitous overexpression of IGEG-2 promotes both vulval induction and sleep, indicating that it is a functional EGF family ligand. The endogenous role of IGEG-2 remains unknown.
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- Award ID(s):
- 2216486
- PAR ID:
- 10636996
- Publisher / Repository:
- microPublication Biology
- Date Published:
- Journal Name:
- microPublication biology
- Volume:
- 2025
- ISSN:
- 2578-9430
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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