Cancer progression is mediated by proline catabolism in non-small cell lung cancer.
Yating LiuChao MaoMin WangNa LiuLianlian OuyangShouping LiuHaosheng TangYa CaoShuang LiuXiang WangDesheng XiaoCeshi ChenYing ShiQin YanKonstantin M J SparrerPublished in: Oncogene (2020)
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.
Keyphrases
- small cell lung cancer
- genome wide
- advanced non small cell lung cancer
- papillary thyroid
- epithelial mesenchymal transition
- brain metastases
- single cell
- dna methylation
- squamous cell
- oxidative stress
- gene expression
- poor prognosis
- dna damage
- epidermal growth factor receptor
- transcription factor
- cell therapy
- stem cells
- squamous cell carcinoma
- binding protein
- bone marrow
- tyrosine kinase