WCLC 2025 - Posters & ePosters-EP.02.01 Investigating the MET Exon 14 Interactome in Lung Adenocarcinoma

Pdf Summary

This study investigates the interactome of MET exon 14 skipping mutants (METex14) in lung adenocarcinoma (LUAD) to understand how altered protein interactions contribute to its oncogenic potential. METex14 arises from splice site mutations in the HGF receptor (MET) that remove exon 14, resulting in mutant proteins with increased stability and half-life. Although METex14’s role in LUAD is known to involve enhanced signaling, prior research focused mainly on its prolonged presence rather than differences in downstream interactions compared to wildtype (WT) MET.<br /><br />The objective of this research is to characterize the METex14 interactome and identify pathway effectors responsible for its tumorigenic activity. The authors applied V5 tagging and lentiviral transduction to express MET WT and METex14 in cells, followed by co-immunoprecipitation and mass spectrometry to capture and quantify protein interactors. Results show that METex14 has distinct binding capacities relative to MET WT, notably displaying increased affinity for the downstream signaling adaptors GAB1 and GRB2, both of which propagate oncogenic RAS/MAPK pathway activation—a previously identified preferential signaling route for METex14.<br /><br />Samples were processed in triplicate to ensure data robustness, with quantitative normalization against bait protein and MET WT intensities. Future work will involve functional validation via knockdown cell line models and signaling assays to dissect the roles of these interactors in METex14-driven oncogenesis.<br /><br />This study enhances understanding of METex14-driven LUAD by elucidating altered protein interactions that may explain its enhanced oncogenic signaling, thus revealing potential therapeutic targets within its unique signaling network.

Asset Subtitle

Sarah Anna Okun

Meta Tag

Speaker Sarah Anna Okun

Topic Tumor Biology – Preclinical Biology

Keywords

MET exon 14 skipping

lung adenocarcinoma

METex14 interactome

protein interactions

oncogenic signaling

GAB1

GRB2

RAS/MAPK pathway

mass spectrometry

therapeutic targets