| Literature DB >> 31911619 |
Yating Liu1,2, Chao Mao1,2, Min Wang1,2, Na Liu1,2, Lianlian Ouyang1,2, Shouping Liu1,2, Haosheng Tang1,2, Ya Cao1, Shuang Liu3, Xiang Wang4, Desheng Xiao5, Ceshi Chen6, Ying Shi7,8, Qin Yan9, Yongguang Tao10,11,12.
Abstract
Dysregulated metabolism contributes to cancer initiation and progression, but the key drivers of these pathways are just being discovered. Here, we report a critical role for proline catabolism in non-small cell lung cancer (NSCLC). Proline dehydrogenase (PRODH) is activated to reduce proline levels by the chromatin remodeling factor lymphoid-specific helicase (LSH), an epigenetic driver of NSCLC. PRODH promotes NSCLC tumorigenesis by inducing epithelial to mesenchymal transition (EMT) and IKKα-dependent inflammatory genes, including CXCL1, LCN2, and IL17C. Consistently, proline addition promotes the expression of these inflammatory genes, as well as EMT, tumor cell proliferation, and migration in vitro and tumor growth in vivo, while the depletion or inhibition of PRODH blocks these phenotypes. In summary, we reveal an essential metabolic pathway amenable to targeting in NSCLC.Entities:
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Year: 2020 PMID： 31911619 DOI： 10.1038/s41388-019-1151-5
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867