Lin28 enhances de novo fatty acid synthesis to promote cancer progression via SREBP‐1. (5th August 2019)

• Record Type: Journal Article
• Authors: Zhang, Yang; Li, Chenchen; Hu, Chuanzhen; Wu, Qian; Cai, Yongping; Xing, Songge; Lu, Hui; Wang, Lin; Huang, De; Sun, Linchong; Li, Tingting; He, Xiaoping; Zhong, Xiuying; Wang, Junfeng; Gao, Ping; Smith, Zachary J; Jia, Weidong; Zhang, Huafeng
• Is Part Of: EMBO reports. Volume 20:Number 10(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-08-05
• Subjects: de novo fatty acid synthesis -- Lin28 -- lipotoxicity -- saturated and unsaturated fatty acids -- SREBP cleavage‐activating protein -- SREBP‐1; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201948115
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Lin28 plays an important role in promoting tumor development, whereas its exact functions and underlying mechanisms are largely unknown. Here, we show that both human homologs of Lin28 accelerate de novo fatty acid synthesis and promote the conversion from saturated to unsaturated fatty acids via the regulation of SREBP‐1. By directly binding to the mRNAs of both SREBP‐1 and SCAP, Lin28A/B enhance the translation and maturation of SREBP‐1, and protect cancer cells from lipotoxicity. Lin28A/B‐stimulated tumor growth is abrogated by SREBP‐1 inhibition and by the impairment of the RNA binding properties of Lin28A/B, respectively. Collectively, our findings uncover that post‐transcriptional regulation by Lin28A/B enhances de novo fatty acid synthesis and metabolic conversion of saturated and unsaturated fatty acids via SREBP‐1, which is critical for cancer progression. Synopsis: Post‐transcriptional regulation by Lin28A and Lin28B enhances de novo fatty acid synthesis and metabolic conversion of saturated and unsaturated fatty acids via SREBP‐1, thereby promoting tumor progression. Lin28A and Lin28B promote de novo fatty acid synthesis. Lin28A/B enhance SREBP‐1 translation and maturation by binding SREBP‐1 and SCAP mRNAs. Lin28A/B protect cancer cells from ER stress. SREBP‐1 is critical for Lin28A/B‐mediated tumor proliferation. Abstract : Post‐transcriptional regulation by Lin28A and Lin28B enhances de novo fatty acid synthesis and metabolic conversion of saturated and unsaturated fatty acids via SREBP‐1, thereby promoting tumor progression.