| Literature DB >> 25936644 |
Fuming Li1, Xiangkun Han1, Fei Li1, Rui Wang2, Hui Wang3, Yijun Gao1, Xujun Wang4, Zhaoyuan Fang1, Wenjing Zhang1, Shun Yao1, Xinyuan Tong1, Yuetong Wang1, Yan Feng1, Yihua Sun2, Yuan Li2, Kwok-Kin Wong5, Qiwei Zhai3, Haiquan Chen6, Hongbin Ji7.
Abstract
LKB1 regulates both cell growth and energy metabolism. It remains unclear how LKB1 inactivation coordinates tumor progression with metabolic adaptation in non-small cell lung cancer (NSCLC). Here in Kras(G12D);Lkb1(lox/lox) (KL) mouse model, we reveal differential reactive oxygen species (ROS) levels in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). ROS can modulate ADC-to-SCC transdifferentiation (AST). Further, pentose phosphate pathway deregulation and impaired fatty acid oxidation collectively contribute to the redox imbalance and functionally affect AST. Similar tumor and redox heterogeneity also exist in human NSCLC with LKB1 inactivation. In preclinical trials toward metabolic stress, certain KL ADC can develop drug resistance through squamous transdifferentiation. This study uncovers critical redox control of tumor plasticity that may affect therapeutic response in NSCLC.Entities:
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Year: 2015 PMID： 25936644 PMCID： PMC4746728 DOI： 10.1016/j.ccell.2015.04.001
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743