Research Papers:

Role and regulation of Yap in KrasG12D-induced lung cancer

Yaopan Mao, Shuguo Sun and Kenneth D. Irvine _

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Oncotarget. 2017; 8:110877-110889. https://doi.org/10.18632/oncotarget.22865

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Yaopan Mao1,*, Shuguo Sun1,2,* and Kenneth D. Irvine1

1Waksman Institute, Cancer Institute of New Jersey, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA

2Current address: Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

*These authors contributed equally to this work

Correspondence to:

Kenneth D. Irvine, email: [email protected]

Keywords: YAP; Kras; adenocarcinoma; lung cancer

Abbreviations: Aveolar type 2: AT2; Epidermal Growth Factor Receptor: EGFR; Atypical adenomatous hyperplasia: AAH; Surfactant protein C: SpC.

Received: September 22, 2017     Accepted: November 05, 2017     Published: December 02, 2017


The Hippo pathway and its downstream transcriptional co-activator Yap influence lung cancer, but the nature of the Yap contribution has been unclear. Using a genetically engineered mouse lung cancer model, we show that Yap deletion completely blocks KrasG12D and p53 loss-driven adenocarcinoma initiation and progression, whereas heterozygosity for Yap partially suppresses lung cancer growth and progression. We also characterize Yap expression during tumor progression and find that nuclear Yap can be detected from the earliest stages of lung carcinogenesis, but at levels comparable to that in aveolar type II cells, which are a cell of origin for lung adenocarcinoma. At later stages of tumorigenesis, variations in Yap levels are detected, which correlate with differences in cell proliferation within tumors. Our observations imply that Yap is not directly activated by oncogenic Kras during lung tumorigenesis, but is nonetheless absolutely required for this tumorigenesis, and support Yap as a therapeutic target in lung adenocarcinoma.

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