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

Yating Liu; Chao Mao; Min Wang; Na Liu; Lianlian Ouyang; Shouping Liu; Haosheng Tang; Ya Cao; Shuang Liu; Xiang Wang; Desheng Xiao; Ceshi Chen; Ying Shi; Qin Yan; Yongguang Tao

doi:10.1038/s41388-019-1151-5

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

Oncogene. 2020 Mar;39(11):2358-2376. doi: 10.1038/s41388-019-1151-5. Epub 2020 Jan 7.

Authors

Yating Liu^{1

2}, Chao Mao^{1

2}, Min Wang^{1

2}, Na Liu^{1

2}, Lianlian Ouyang^{1

2}, Shouping Liu^{1

2}, Haosheng Tang^{1

2}, Ya Cao¹, Shuang Liu³, Xiang Wang⁴, Desheng Xiao⁵, Ceshi Chen⁶, Ying Shi^{7

8}, Qin Yan⁹, Yongguang Tao^{10

11

12}

Affiliations

¹ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China.
² NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China.
³ Department of Oncology, Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁴ Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
⁵ Department of Pathology, School of Basic Medicine and Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
⁶ Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Collaborative Innovation Center for Cancer Medicine, Kunming, Yunnan, 650223, China.
⁷ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China. yingshi@csu.edu.cn.
⁸ NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China. yingshi@csu.edu.cn.
⁹ Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, USA. qin.yan@yale.edu.
¹⁰ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, China. taoyong@csu.edu.cn.
¹¹ NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, 410078, China. taoyong@csu.edu.cn.
¹² Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011, China. taoyong@csu.edu.cn.

PMID: 31911619
DOI: 10.1038/s41388-019-1151-5

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Disease Progression
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Mice
Proline / metabolism*
Transfection

Substances

Proline