title: Control of alveolar differentiation by the lineage transcription factors GATA6 and HOPX inhibits lung adenocarcinoma metastasis.
abstract: Molecular programs that mediate normal cell differentiation are required for oncogenesis and tumor cell survival in certain cancers. How cell-lineage-restricted genes specifically influence metastasis is poorly defined. In lung cancers, we uncovered a transcriptional program that is preferentially associated with distal airway epithelial differentiation and lung adenocarcinoma (ADC) progression. This program is regulated in part by the lineage transcription factors GATA6 and HOPX. These factors can cooperatively limit the metastatic competence of ADC cells, by modulating overlapping alveolar differentiation and invasogenic target genes. Thus, GATA6 and HOPX are critical nodes in a lineage-selective pathway that directly links effectors of airway epithelial specification to the inhibition of metastasis in the lung ADC subtype.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: William K C
authors.initials: WK
authors.lastname: Cheung
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhao
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Laura E
authors.initials: LE
authors.lastname: Stevens
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cao
authors.forename: Justin E
authors.initials: JE
authors.lastname: Fang
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Westbrook
authors.forename: Don X
authors.initials: DX
authors.lastname: Nguyen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D016000:Cluster Analysis; D004848:Epithelium / Q000473:pathology; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C476884:HOPX protein, human; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins