Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2

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Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2

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Title: Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
Author: Zhang, Haikuo; Fillmore Brainson, Christine; Koyama, Shohei; Redig, Amanda J.; Chen, Ting; Li, Shuai; Gupta, Manav; Garcia-de-Alba, Carolina; Paschini, Margherita; Herter-Sprie, Grit S.; Lu, Gang; Zhang, Xin; Marsh, Bryan P.; Tuminello, Stephanie J.; Xu, Chunxiao; Chen, Zhao; Wang, Xiaoen; Akbay, Esra A.; Zheng, Mei; Palakurthi, Sangeetha; Sholl, Lynette M.; Rustgi, Anil K.; Kwiatkowski, David J.; Diehl, J Alan; Bass, Adam J.; Sharpless, Norman E.; Dranoff, Glenn; Hammerman, Peter S.; Ji, Hongbin; Bardeesy, Nabeel; Saur, Dieter; Watanabe, Hideo; Kim, Carla F.; Wong, Kwok-Kin

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhang, H., C. Fillmore Brainson, S. Koyama, A. J. Redig, T. Chen, S. Li, M. Gupta, et al. 2017. “Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2.” Nature Communications 8 (1): 14922. doi:10.1038/ncomms14922. http://dx.doi.org/10.1038/ncomms14922.
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Abstract: Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours.
Published Version: doi:10.1038/ncomms14922
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385585/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630627
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