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

@inproceedings{Zhang2017Lkb1ID,
  title={Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2},
  author={Haikuo Zhang and Christine Fillmore Brainson and Syohei Koyama and Amanda J. Redig and Ting Chen and Shuai Li and Manav Gupta and Carolina Garcia-de-Alba and Margherita Paschini and Grit Sophie Herter-Sprie and Gang Lu and Xin Zhang and Bryan P. Marsh and Stephanie J. Tuminello and Chunxiao Xu and Zhao Chen and Xiaoen Wang and Esra A. Akbay and Mei Qin Zheng and Sangeetha Palakurthi and Lynette M Sholl and Anil K Rustgi and David J Kwiatkowski and J Alan Diehl and Adam J. Bass and Norman E Sharpless and Glenn Dranoff and Peter S. Hammerman and Hongbin Ji and Nabeel Bardeesy and Dieter Saur and Hideo Watanabe and Carla F Kim and Kwok-kin Wong},
  booktitle={Nature communications},
  year={2017}
}
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… CONTINUE READING
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