{"doi":"10.1016/j.celrep.2021.109905","title":"FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma","abstract":"Despite the undisputable role of the small GTPase Rac1 in the regulation of actin cytoskeleton reorganization, the Rac guanine-nucleotide exchange factors (Rac-GEFs) involved in Rac1-mediated motility and invasion in human lung adenocarcinoma cells remain largely unknown. Here, we identify FARP1, ARHGEF39, and TIAM2 as essential Rac-GEFs responsible for Rac1-mediated lung cancer cell migration upon EGFR and c-Met activation. Noteworthily, these Rac-GEFs operate in a non-redundant manner by controlling distinctive aspects of ruffle dynamics formation. Mechanistic analysis reveals a leading role of the AXL-Gab1-PI3K axis in conferring pro-motility traits downstream of EGFR. Along with the positive association between the overexpression of Rac-GEFs and poor lung adenocarcinoma patient survival, we show that FARP1 and ARHGEF39 are upregulated in EpCam+ cells sorted from primary human lung adenocarcinomas. Overall, our study reveals fundamental insights into the complex intricacies underlying Rac-GEF-mediated cancer cell motility signaling, hence underscoring promising targets for metastatic lung cancer therapy.","journal":"Cell Reports","year":2021,"id":164012,"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":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":413697,"name":"Gabriel Kreider-Letterman","orcid":"0000-0002-3081-6698","position":1,"is_corresponding":false},{"id":402300,"name":"Martin J. Baker","orcid":"0000-0002-9743-6294","position":2,"is_corresponding":false},{"id":684658,"name":"Suli Zhang","orcid":"0000-0003-4894-1160","position":3,"is_corresponding":false},{"id":403835,"name":"Neil T. Sullivan","orcid":"0000-0002-4589-9182","position":4,"is_corresponding":false},{"id":231764,"name":"Evgeniy Eruslanov","orcid":"0000-0003-0743-5026","position":5,"is_corresponding":false},{"id":375972,"name":"Martı́n C. Abba","orcid":"0000-0002-9206-2369","position":6,"is_corresponding":false},{"id":526987,"name":"Silvia M. Goicoechea","orcid":"0000-0003-1107-389X","position":7,"is_corresponding":false},{"id":402301,"name":"Rafael García‐Mata","orcid":"0000-0002-7116-4411","position":8,"is_corresponding":false},{"id":402302,"name":"Marcelo G. Kazanietz","orcid":"0000-0001-8779-017X","position":9,"is_corresponding":false},{"id":413696,"name":"Mariana Cooke","orcid":"0000-0001-9300-8447","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T23:45:27.031465Z","pmid":"34731623","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":[]}