The UDP-glucose ceramide glycosyltransferase (UGCG) and the link to multidrug resistance protein 1 (MDR1).
Marthe-Susanna WegnerLisa GruberPeter MattjusGerd GeisslingerSabine GröschPublished in: BMC cancer (2018)
The UDP-glucose ceramide glycosyltransferase (UGCG) is a key enzyme in the sphingolipid metabolism by generating glucosylceramide (GlcCer), the precursor for all glycosphingolipids (GSL), which are essential for proper cell function. Interestingly, the UGCG is also overexpressed in several cancer types and correlates with multidrug resistance protein 1 (MDR1) gene expression. This membrane protein is responsible for efflux of toxic substances and protects cancer cells from cell damage through chemotherapeutic agents. Studies showed a connection between UGCG and MDR1 overexpression and multidrug resistance development, but the precise underlying mechanisms are unknown. Here, we give an overview about the UGCG and its connection to MDR1 in multidrug resistant cells. Furthermore, we focus on UGCG transcriptional regulation, the impact of UGCG on cellular signaling pathways and the effect of UGCG and MDR1 on the lipid composition of membranes and how this could influence multidrug resistance development. To our knowledge, this is the first review presenting an overview about UGCG with focus on the relationship to MDR1 in the process of multidrug resistance development.
Keyphrases
- multidrug resistant
- drug resistant
- gram negative
- acinetobacter baumannii
- gene expression
- klebsiella pneumoniae
- papillary thyroid
- signaling pathway
- healthcare
- induced apoptosis
- dna methylation
- oxidative stress
- type diabetes
- blood glucose
- stem cells
- protein protein
- adipose tissue
- cell therapy
- single cell
- lymph node metastasis
- blood pressure
- young adults
- childhood cancer
- metabolic syndrome
- bone marrow
- cell death