Details

Autor(en) / Beteiligte

• Caetano, Mauricio S
• Hassane, Maya
• Van, Hieu T
• Bugarin, Emmanuel
• Cumpian, Amber M
• McDowell, Christina L
• Cavazos, Carolina Gonzalez
• Zhang, Huiyuan
• Deng, Shanshan
• Diao, Lixia
• Wang, Jing
• Evans, Scott E
• Behrens, Carmen
• Wistuba, Ignacio I
• Fuqua, Susan A W
• Lin, Huang
• Stabile, Laura P
• Watowich, Stephanie S
• Kadara, Humam
• Moghaddam, Seyed Javad

Titel

Sex specific function of epithelial STAT3 signaling in pathogenesis of K-ras mutant lung cancer

Ist Teil von

• Nature communications, 2018-11, Vol.9 (1), p.4589-11, Article 4589

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Lung adenocarcinomas (LUADs) with mutations in the K-ras oncogene display dismal prognosis. Proinflammatory and immunomodulatory events that drive development of K-ras mutant LUAD are poorly understood. Here, we develop a lung epithelial specific K-ras mutant/Stat3 conditional knockout (LR/Stat3 ) mouse model. Epithelial Stat3 deletion results in intriguing sex-associated discrepancies; K-ras mutant tumors are decreased in female LR/Stat3 mice whereas tumor burdens are increased in males. RNA-sequencing and tumor microenvironment (TME) analysis demonstrate increased anti-tumor immune responses following Stat3 deletion in females and, conversely, elevated pro-tumor immune pathways in males. While IL-6 blockade in male LR/Stat3 mice reduces lung tumorigenesis, inhibition of estrogen receptor signaling in female mice augments K-ras mutant oncogenesis and reprograms lung TME toward a pro-tumor phenotype. Our data underscore a critical sex-specific role for epithelial Stat3 signaling in K-ras mutant LUAD, thus paving the way for developing personalized (e.g. sex-based) immunotherapeutic strategies for this fatal disease.