{"doi":"10.1101/2020.01.29.924449","title":"FCHSD2 Controls Oncogenic ERK1/2 Signaling Outcome by Regulating Endocytic Trafficking","abstract":"Abstract Cancer progression is driven, in part, by altered signaling downstream of receptor tyrosine kinases (RTKs). Surface expression and RTK activity are regulated by clathrin-mediated endocytosis (CME), endosomal recycling or degradation. In turn, oncogenic signaling downstream of RTKs can reciprocally regulate endocytic trafficking, creating feedback loops that enhance tumor progression. We previously reported a cancer-cell specific function of FCHSD2 (FCH/F-BAR and double SH3 domain-containing protein) in regulating CME in non-small-cell lung cancer (NSCLC) cells. Here, we report that FCHSD2 loss impacts recycling of EGFR and MET, diverting their trafficking toward late endosomes and lysosomes. FCHSD2 depletion results in the nuclear translocation of active ERK1/2, leading to enhanced transcription and upregulation of EGFR and MET. The small GTPase, Rab7, is essential for the FCHSD2 depletion-induced effects. Correspondingly, FCHSD2 loss correlates with higher tumor grades of NSCLC. Clinically, NSCLC patients expressing high FCHSD2 exhibit elevated survival, whereas patients with high Rab7 expression display decreased survival rates. Our study provides new insight into the molecular nexus for crosstalk between oncogenic signaling and RTK trafficking that controls cancer progression.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124587,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":274920,"name":"Sandra L. Schmid","orcid":"0000-0002-1690-7024","position":1,"is_corresponding":false},{"id":406591,"name":"Guan-Yu Xiao","orcid":"0000-0003-3454-6717","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}