{"doi":"10.32388/ccylg3","title":"Kinase Suppressor of Ras 2 Promotes Self-Renewal and Clonogenicity of Small-Cell Lung Carcinoma","abstract":"Small-cell lung carcinoma (SCLC) tumors are heterogeneous, with a subpopulation of cells primed for tumor initiation. Here, we show that Kinase Suppressor of Ras 2 (KSR2) promotes the self-renewal and clonogenicity of SCLC cells. KSR2 is a molecular scaffold that promotes Raf/MEK/ERK signaling. KSR2 is preferentially expressed in the ASCL1 subtype of SCLC (SCLC-A) tumors and is expressed in pulmonary neuroendocrine cells, one of the identified cells of origin for SCLC-A tumors. The expression of KSR2 in SCLC and pulmonary neuroendocrine cells (PNECs) was previously unrecognized and serves as a novel model for understanding the role of KSR2-dependent signaling in normal and malignant tissues. Disruption of KSR2 in SCLC-A cell lines inhibits the colony forming ability of tumor propagating cells (TPCs) _in vitro_ and their tumor initiating capacity _in vivo._ The effect of KSR2 depletion on self-renewal and clonogenicity is dependent on the interaction of KSR2 with ERK. These data indicate that the expression of KSR2 is an essential driver of SCLC-A tumor propagating cell function, and therefore may play a role in SCLC tumor initiation. These findings shed light on a novel effector promoting initiation of ASCL1-subtype SCLC tumors, and a potential subtype-specific therapeutic target.","journal":"Qeios","year":2025,"id":561094,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":991264,"name":"Deepan Chatterjee","orcid":"0000-0001-7997-7014","position":1,"is_corresponding":false},{"id":302443,"name":"Abbie S. Ireland","orcid":"0000-0002-4178-7239","position":2,"is_corresponding":false},{"id":1245536,"name":"Sydney A. Skupa","orcid":null,"position":3,"is_corresponding":false},{"id":253870,"name":"Luc Girard","orcid":"0000-0002-6688-5281","position":4,"is_corresponding":false},{"id":566251,"name":"Kurt W. Fisher","orcid":"0000-0002-8391-390X","position":5,"is_corresponding":false},{"id":351574,"name":"Michael S. Kareta","orcid":"0000-0002-6980-9065","position":6,"is_corresponding":false},{"id":71347,"name":"John D. Minna","orcid":"0000-0002-7776-0767","position":7,"is_corresponding":false},{"id":6196,"name":"Trudy G. Oliver","orcid":"0000-0003-2082-2397","position":8,"is_corresponding":false},{"id":566250,"name":"Robert E. Lewis","orcid":"0000-0002-3616-2971","position":9,"is_corresponding":false},{"id":991263,"name":"Dianna H. Huisman","orcid":"0000-0002-1183-5391","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:55:46.921885Z","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":[]}