Soluble, but not precursor EGF induces intracrine signaling of the EGFR
Bilakovics, N.; Volko, J.; Jeppesen, C.; Fekete, G. J.; Csomos, I.; Bodnar, A.; Mocsar, G.; Nemeth, K.; Kormos, A.; Toth, K.; Vereb, G.; Nagy, P.; Vamosi, G.
Show abstract
EGFR is a transmembrane receptor tyrosine kinase regulating growth and survival in epithelial tissues. Its ligand, the epidermal growth factor (EGF), is produced as a membrane-anchored precursor (preEGF) that is proteolytically cleaved to release soluble EGF (sEGF). EGFR overexpression can convert it from a physiological regulator into an oncogenic driver. Therapeutic strategies targeting EGFR include monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). Although mAbs such as cetuximab initially block EGFR activity, tumors often develop resistance. Recent findings indicate that sEGF can activate EGFR within intracellular vesicles, promoting intracrine signaling that sustains proliferation despite extracellular inhibition. Here, we investigated the mechanism of intracrine EGFR signaling in the Golgi apparatus using confocal microscopy, FRET and fluorescence correlation spectroscopy. sEGF, but not preEGF, bound and induced EGFR dimerization and phosphorylation. Erlotinib, a membrane permeable TKI, effectively blocked phosphorylation, whereas extracellular cetuximab did not. These findings imply sEGF-induced intracrine EGFR signaling in the Golgi. Our results may shed light on a potential resistance mechanism to antibody treatment.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Centrosomal P4.1-associated protein (CPAP) positively regulates endocytic vesicular transport and lysosome targeting of EGFR 94%
- Repeated FRAP of the actin-binding protein CapG in the cell nucleus - a functional assay for EGF signaling in the single live breast cancer cell 94%
- Characterization of clostridium botulinum neurotoxin serotype A (BoNT/A) and fibroblast growth factor receptor interactions using a novel receptor dimerization assay 93%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Redundant and specific roles of EGFR ligands in the ERK activation waves during collective cell migration of MDCK cells 94%
- Small disulfide loops in peptide hormones mediate self-aggregation and secretory granule sorting 93%
- The concerted action of SEPT9 and EPLIN modulates the adhesion and migration of human fibroblasts 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.