4.6 Article

SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2016.05.011

关键词

SND1; Hepatoma; Cholesterol; SREBP2; Cancer metabolism

资金

  1. SGIker (Analytical and High-Resolution Microscopy in Biomedicine Service) of the University of the Basque Country UPV/EHU
  2. Basque Country Government (Saiotek) [SA-2010/00050, IT-336-10, AE-2012-1-69]
  3. University of the Basque Country UPV/EHU [UFI11/20]
  4. Jesus de Gangoiti Barrera Foundation
  5. Basque Country Government

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SND1 is a multifunctional protein participating, among others, in gene transcription and mRNA metabolism. SND1 is overexpressed in cancer cells and promotes viability and tumourigenicity of hepatocellular carcinoma cells. This study shows that cholesterol synthesis is increased in SND1-overexpressing hepatoma cells. Neither newly synthesised nor extracellularly supplied cholesterol are able to suppress this increase; however, inhibition of cholesterol esterification reverted the activated state of sterol-regulatory element-binding protein 2 (SREBP2) and cholesterogenesis. These results highlight SND1 as a potential regulator of cellular cholesterol distribution and homeostasis in hepatoma cells, and support the rationale for the therapeutic use of molecules that influence cholesterol management when SND1 is overexpressed. (C) 2016 Elsevier B.V. All rights reserved.

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