{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Concepcion CP"],"funding":["American Cancer Society","Koch Institute Cancer Center Support","EPA","Mission Boost Grant","NCI NIH HHS","Memorial Sloan Kettering Cancer Center","NIH"],"pagination":["562-585"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8831463"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(2)"],"pubmed_abstract":["<i>SMARCA4</i>/<i>BRG1</i> encodes for one of two mutually exclusive ATPases present in mammalian SWI/SNF chromatin remodeling complexes and is frequently mutated in human lung adenocarcinoma. However, the functional consequences of <i>SMARCA4</i> mutation on tumor initiation, progression, and chromatin regulation in lung cancer remain poorly understood. Here, we demonstrate that loss of <i>Smarca4</i> sensitizes club cell secretory protein-positive cells within the lung in a cell type-dependent fashion to malignant transformation and tumor progression, resulting in highly advanced dedifferentiated tumors and increased metastatic incidence. Consistent with these phenotypes, <i>Smarca4</i>-deficient primary tumors lack lung lineage transcription factor activities and resemble a metastatic c"],"journal":["Cancer discovery"],"pubmed_title":["<i>Smarca4</i> Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung."],"pmcid":["PMC8831463"],"funding_grant_id":["P30-CA14051","EP-C-17-009","PF-17-009-01-CDD","R01 CA216188","P30 CA008748","P30 CA014051","MBG-18-204-01-COUN","P30-CA008748","R01CA216188","P01 Jacks P01-CA42063","P01 CA042063"],"pubmed_authors":["Kim CF","Ma S","Bhutkar A","Miller M","Liu M","Meli K","LaFave LM","DeAngelo LP","Del Priore I","Westcott PMK","Rekhtman N","Jacks T","Sanchez-Rivera FJ","Kim JY","Regev A","Schoenfeld AJ","Buenrostro JD","Concepcion CP","Kartha VK","Riely GJ","Bronson RT","Rudin CM","Gupta M"],"additional_accession":[]},"is_claimable":false,"name":"<i>Smarca4</i> Inactivation Promotes Lineage-Specific Transformation and Early Metastatic Features in the Lung.","description":"<i>SMARCA4</i>/<i>BRG1</i> encodes for one of two mutually exclusive ATPases present in mammalian SWI/SNF chromatin remodeling complexes and is frequently mutated in human lung adenocarcinoma. However, the functional consequences of <i>SMARCA4</i> mutation on tumor initiation, progression, and chromatin regulation in lung cancer remain poorly understood. Here, we demonstrate that loss of <i>Smarca4</i> sensitizes club cell secretory protein-positive cells within the lung in a cell type-dependent fashion to malignant transformation and tumor progression, resulting in highly advanced dedifferentiated tumors and increased metastatic incidence. Consistent with these phenotypes, <i>Smarca4</i>-deficient primary tumors lack lung lineage transcription factor activities and resemble a metastatic c","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2026-05-08T11:30:48.213Z","creation":"2025-04-19T06:04:40.677Z"},"accession":"S-EPMC8831463","cross_references":{"pubmed":["34561242"],"doi":["10.1158/2159-8290.cd-21-0248","10.1158/2159-8290.CD-21-0248"]}}