Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Metabolic reprogramming endows cancer cells with the ability to adjust metabolic pathways to support heterogeneously biological processes. However, it is not known how the reprogrammed activities are implemented during differentiation of cancer stem cells (CSCs). In this study, we demonstrated that liver CSCs relied on the enhanced mitochondrial function to maintain stemness properties, which is different from aerobic glycolysis playing main roles in the differentiated non-CSCs. We found that liver CSCs exhibit increased mitochondrial respiratory capacity and that complex-I of mitochondria was necessary for stemness properties of liver CSCs through regulation of mitochondrial respiration. Bioinformatics analysis reveals that
mitochondrial ribosomal protein S5
(
MRPS5
) is closely related with the function of complex-I. Further experiments confirmed that
MRPS5
promoted the production of nicotinamide adenine dinucleotide (NAD
+
), which is necessary for enhanced mitochondrial function in liver CSCs.
MRPS5
played a critical role for liver CSCs to maintain stemness properties and to participate in tumor progression. Mechanistically, the acetylation status of
MRPS5
is directly regulated by NAD
+
dependent deacetylase sirtuin-1 (SIRT1), which is abundant in liver CSCs and decreased during differentiation. Deacetylated
MRPS5
locates in mitochondria to promote the function complex-I and the generation of NAD
+
to enhance mitochondrial respiration. Conversely, the acetylated
MRPS5
gathered in nuclei leads to increased expression of glycolytic proteins and promotion of the Warburg Effect. Therefore, liver CSCs transform mitochondrial-dependent energy supply to a Warburg phenotype by the dual function of
MRPS5
. Clinical analysis of SIRT1 and
MRPS5
expression in tumor tissues showed the SIRT1
High
/Cytoplasmic-
MRPS5
High
profile was associated with patients with
hepatocellular carcinoma
with poor prognosis. Conclusion: SIRT1/
MRPS5
axis participates in metabolic reprogramming to facilitate tumor progression and may serve as a promising therapeutic target of liver cancer.
...
PMID:Sirtuin-1/Mitochondrial Ribosomal Protein S5 Axis Enhances the Metabolic Flexibility of Liver Cancer Stem Cells. 3090 Oct 96
