Time-resolved phenotypic profiling maps EGFR and c-Met trafficking signatures
- 1Institute for Comprehensive Medical Sciences, Tokyo Women’s Medical University
Abstract
The epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met/MET) are receptor tyrosine kinases (RTKs) whose signalling depends on endocytic routing, and impaired down-regulation can drive tumour progression and therapy resistance, including MET-driven bypass of EGFR inhibition. However, how routing states couple to signalling and lipid programs, and how this differs between receptors under matched conditions, remains unclear. Using a chemically diverse annotated inhibitor library, we performed time-resolved, pathway-focused high-content imaging in A549 cells to compare co-varying phenotypes across matched EGFR and c-Met assay systems. Late receptor persistence defined operational degradation-inhibitor phenotypes that were heterogeneous and dispersed across a fused phenotypic atlas. Despite this heterogeneity, matched degradation-inhibitor sets showed receptor-selective lipid–trafficking coupling: EGFR persistence was associated with reduced phosphatidylinositol 4,5-bisphosphate-linked readouts and signalling biases, whereas c-Met persistence aligned with increased perinuclear phosphatidylinositol 4-phosphate heterogeneity and altered transferrin-recycling readouts. These results provide a comparative imaging framework for mapping RTK trafficking states and nominate phosphoinositide-linked features as candidate readouts of trafficking rewiring in cancer-relevant contexts.
Related
- Time-resolved transcriptomic profiling of Dictyostelium discoideum infection with Mycobacterium marinum reveals Atg9-dependent restriction via maintenance of vacuole integrity
- Localis-REX: a general protocol for time-resolved spatiofunctional profiling in live cells and C. elegans
- Traffickome infers directed, compartment-resolved membrane trafficking from proteomic data
- Metabolomic Profiling Screening for Molecular Level Associations Related to Cashmere Quality Related Phenotypic Types in Liaoning Cashmere Goats
- Identification of a putative RocS homolog through phenotypic profiling of uncharacterized essential genes in Streptococcus mutans
BibTeX
@article{tanabe2026timeresolved,
title = {{Time-resolved phenotypic profiling maps EGFR and c-Met trafficking signatures}},
author = {Kenji Tanabe},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-61308-w},
url = {https://doi.org/10.1038/s41598-026-61308-w},
note = {CC BY},
}
RIS
TY - JOUR
TI - Time-resolved phenotypic profiling maps EGFR and c-Met trafficking signatures
AU - Kenji Tanabe
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-61308-w
UR - https://doi.org/10.1038/s41598-026-61308-w
AB - The epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met/MET) are receptor tyrosine kinases (RTKs) whose signalling depends on endocytic routing, and impaired down-regulation can drive tumour progression and therapy resistance, including MET-driven bypass of EGFR inhibition. However, how routing states couple to signalling and lipid programs, and how this differs between receptors under matched conditions, remains unclear. Using a chemically diverse annotated inhibitor library, we performed time-resolved, pathway-focused high-content imaging in A549 cells to compare co-varying phenotypes across matched EGFR and c-Met assay systems. Late receptor persistence defined operational degradation-inhibitor phenotypes that were heterogeneous and dispersed across a fused phenotypic atlas. Despite this heterogeneity, matched degradation-inhibitor sets showed receptor-selective lipid–trafficking coupling: EGFR persistence was associated with reduced phosphatidylinositol 4,5-bisphosphate-linked readouts and signalling biases, whereas c-Met persistence aligned with increased perinuclear phosphatidylinositol 4-phosphate heterogeneity and altered transferrin-recycling readouts. These results provide a comparative imaging framework for mapping RTK trafficking states and nominate phosphoinositide-linked features as candidate readouts of trafficking rewiring in cancer-relevant contexts.
SN - 2045-2322
ER -