Cancer progression is mediated by proline catabolism in non-small cell lung cancer

Release time:2020-07-12

Impact Factor:7.971

Affiliation of Author(s):中南大学

Teaching and Research Group:病理学系

Journal:oncogene

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.

Co-author:Chao Mao, Min Wang, Na Liu, Lianlian Ouyang, Shouping Liu, Haosheng Tang, Ya Cao, Shuang Liu, Xiang Wang, Desheng Xiao, Ceshi Chen

First Author:Yating Liu

Indexed by:Journal paper

Correspondence Author:Ying Shi, Qin Yan, Yongguang Tao

Issue:39(11)

Page Number:2358-2376

Translation or Not:no

Date of Publication:2020-01-07

Included Journals:SCI