Lin28 enhances de novo fatty acid synthesis to promote cancer progression via SREBP-1.

EMBO Reports
Yang ZhangHuafeng Zhang

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.

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Citations

Aug 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiao-Jun Li, Angelika Doetzlhofer
Aug 19, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuting MaMinxin Shi
Jul 22, 2021·Journal of Cellular Physiology·Yu-Sheng QinChao-Ke Tang

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