Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cellsReportar como inadecuado




Effect of lentivirus-mediated shRNA inactivation of HK1, HK2, and HK3 genes in colorectal cancer and melanoma cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Genetics

, 17:156

First Online: 22 December 2016DOI: 10.1186-s12863-016-0459-1

Cite this article as: Kudryavtseva, A.V., Fedorova, M.S., Zhavoronkov, A. et al. BMC Genet 2016 17Suppl 3: 156. doi:10.1186-s12863-016-0459-1

Abstract

BackgroundThe switch from oxidative phosphorylation to glycolysis in proliferating cancer cells, even under aerobic conditions, has been shown first in 1926 by Otto Warburg. Today this phenomenon is known as the -Warburg effect- and recognized as a hallmark of cancer. The metabolic shift to glycolysis is associated with the alterations in signaling pathways involved in energy metabolism, including glucose uptake and fermentation, and regulation of mitochondrial functions. Hexokinases HKs, which catalyze the first step of glycolysis, have been identified to play a role in tumorigenesis of human colorectal cancer CRC and melanoma. However, the mechanism of action of HKs in the promotion of tumor growth remains unclear.

ResultsThe purpose of the present study was to investigate the effect of silencing of hexokinase genes HK1, HK2, and HK3 in colorectal cancer HT-29, SW 480, HCT-15, RKO, and HCT 116 and melanoma MDA-MB-435S and SK-MEL-28 cell lines using short hairpin RNA shRNA lentiviral vectors. shRNA lentiviral plasmid vectors pLSLP-HK1, pLSLP-HK2, and pLSLP-HK3 were constructed and then transfected separately or co-transfected into the cells. HK2 inactivation was associated with increased expression of HK1 in colorectal cancer cell lines pointing to the compensation effect. Simultaneous attenuation of HK1 and HK2 levels led to decreased cell viability. Co-transfection with shRNA vectors against HK1, HK2, and HK3 mRNAs resulted in a rapid cell death via apoptosis.

ConclusionsWe have demonstrated that simultaneous inactivation of HK1 and HK2 was sufficient to decrease proliferation and viability of melanoma and colorectal cancer cells. Our results suggest that HK1 and HK2 could be the key therapeutic targets for reducing aerobic glycolysis in examined cancers.

KeywordsWarburg effect Hexokinases shRNA Glycolysis Melanoma Colorectal cancer  Download fulltext PDF



Autor:

Fuente: https://link.springer.com/







Documentos relacionados