SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma
Hiart Navarro-Imaz1, Yuri Rueda1, Olatz Fresnedo1
1Lipids & Liver Research Group, Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Barrio Sarriena SN, Leioa 48940, Spain.
Abstract:
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.
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