Journal article
Alveolar type I cells can give rise to KRAS-induced lung adenocarcinoma
Cell reports, Vol.42(12), 113286
12/26/2023
DOI: 10.1016/j.celrep.2023.113286
PMCID: PMC10842735
PMID: 37995179
Abstract
Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer and presents clinically with a high degree of biological heterogeneity and distinct clinical outcomes. The current paradigm of LUAD etiology posits alveolar epithelial type II (AT2) cells as the primary cell of origin, while the role of AT1 cells in LUAD oncogenesis remains unknown. Here, we examine oncogenic transformation in mouse Gram-domain containing 2 (Gramd2)+ AT1 cells via oncogenic KRASG12D. Activation of KRASG12D in AT1 cells induces multifocal LUAD, primarily of papillary histology. Furthermore, KRT8+ intermediate cell states were observed in both AT2- and AT1-derived LUAD, but SCGB3A2+, another intermediate cell marker, was primarily associated with AT1 cells, suggesting different mechanisms of tumor evolution. Collectively, our study reveals that Gramd2+ AT1 cells can serve as a cell of origin for LUAD and suggests that distinct subtypes of LUAD based on cell of origin be considered in the development of therapeutics.
Details
- Title: Subtitle
- Alveolar type I cells can give rise to KRAS-induced lung adenocarcinoma
- Creators
- Minxiao Yang - University of Southern CaliforniaHua Shen - University of Southern CaliforniaPer Flodby - University of Southern CaliforniaMichael Koss - University of Southern CaliforniaRania Bassiouni - University of Southern CaliforniaYixin Liu - University of Southern CaliforniaTea Jashashvili - University of Southern CaliforniaAaron Neely - University of Southern CaliforniaEzuka Ogbolu - University of Southern CaliforniaJonathan Castillo - University of Southern CaliforniaTheresa Stueve - University of Southern CaliforniaDaniel Mullen - University of Southern CaliforniaAmy Ryan - University of IowaJohn Carpten - University of Southern CaliforniaW Dean Wallace - University of Southern CaliforniaBeiyun Zhou - University of Southern CaliforniaZea Borok - University of California San DiegoCrystal Marconett - University of Southern CaliforniaAlessandra Castaldi - University of Southern California
- Resource Type
- Journal article
- Publication Details
- Cell reports, Vol.42(12), 113286
- DOI
- 10.1016/j.celrep.2023.113286
- PMID
- 37995179
- PMCID
- PMC10842735
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- Publisher
- Cell Press
- Grant note
- DOI: 10.13039/100000048, name: American Cancer Society, award: RSG-20-135-01; DOI: 10.13039/100000050, name: National Heart Lung and Blood Institute, award: R35 HL135747; DOI: 10.13039/100000054, name: National Cancer Institute, award: P30 CA014089, R01 CA262258; DOI: 10.13039/100007850, name: Waitt Foundation, award: U54 CA233444, U54 CA233465, U54 CA23396
- Language
- English
- Date published
- 12/26/2023
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984561557202771
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