Advertisement

Topics

SIRT1/MRPS5 axis enhances the metabolic flexibility of liver cancer stem cells.

08:00 EDT 22nd March 2019 | BioPortfolio

Summary of "SIRT1/MRPS5 axis enhances the metabolic flexibility of liver cancer stem cells."

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 complex-I of mitochondrial was necessary for stemness properties of liver CSCs via 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 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 /Cytoplasmic-MRPS5 profile was associated with poor prognosis hepatocellular carcinoma (HCC) patients. Conclusions: SIRT1/MRPS5 axis participates in metabolic reprogramming to facilitate tumor progression and may serve as a promising therapeutic target of liver cancer. This article is protected by copyright. All rights reserved.

Affiliation

Journal Details

This article was published in the following journal.

Name: Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Pages:

Links

DeepDyve research library

PubMed Articles [24226 Associated PubMed Articles listed on BioPortfolio]

SIRT1 inhibits gastric cancer proliferation and metastasis via STAT3/MMP-13 signaling.

Gastric cancer prognoses are persistently poor due to cancer's penchant to metastasize. As a crucial regulator of signal transducer and activator of transcription (STAT3) signaling, sirtuin 1's (SIRT1...

Improved mass spectrometry-based activity assay reveals oxidative and metabolic stress as sirtuin-1 regulators.

Sirtuin-1 (SirT1) catalyzes NAD-dependent protein lysine deacetylation and is a critical regulator of energy and lipid metabolism, mitochondrial biogenesis, apoptosis, and senescence. Activation of Si...

PCAF fine-tunes hepatic metabolic syndrome, inflammatory disease, and cancer.

The P300/CBP-associating factor (PCAF), a histone acetyltransferase, is involved in metabolic and pathogenic diseases, particularly of the liver. The effects of PCAF on fine-tuning liver diseases are ...

Gα12 ablation exacerbates liver steatosis and obesity by suppressing USP22/SIRT1-regulated mitochondrial respiration.

Non-alcoholic fatty liver disease (NAFLD) arises from mitochondrial dysfunction under sustained imbalance between energy intake and expenditure, but the underlying mechanisms controlling mitochondrial...

Tudca Ameliorates Liver Injury Via Activation of SIRT1-FXR Signaling in a Rat Hemorrhagic Shock Model.

To investigate the changes of bile acids in the liver during hemorrhagic shock (HS) and their potential to attenuate liver injury via activation of SIRT1 (sirtuin 1)-FXR (farnesoid X receptor) signali...

Clinical Trials [15584 Associated Clinical Trials listed on BioPortfolio]

Acute and Chronic Metabolic Flexibility in Individuals Living With Obesity: The i-FLEX Study

Regular exercise is a cornerstone in the prevention and the management of cardio-metabolic risk factors. Some of the beneficial effect of exercise training occurs through metabolic flexibi...

Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber

The overarching aim of this study: To determine the effect of different meal compositions (high- vs. low-fat) on metabolic flexibility as it relates to meal-stimulated (ΔRQ1) and sleep (...

Microvascular Blood Flow and Metabolic Flexibility in Hispanics

Microvascular insulin resistance has been shown to precede myocyte insulin resistance and impairments in metabolic function. However, there is no convincing data showing the relationship b...

Muscle Energy Metabolism and Metabolic Flexibility in Older Men and Women

This study will explore differences in energy metabolism and metabolic flexibility under various conditions in older men and women.

Environmental Factors and the Gut Microbiome - Endocannabinoid Axis

The general objective of this project is to investigate the interplay of the gut microbiome - endocannabinoid axis with host environmental factors and intestinal, metabolic and mental heal...

Medical and Biotech [MESH] Definitions

A human liver tumor cell line used to study a variety of liver-specific metabolic functions.

Tumors or cancer of the LIVER.

Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.

Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed)

The rotational force about an axis that is equal to the product of a force times the distance from the axis where the force is applied.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Hepatology
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Stem Cells
Track and monitor developments in stem cell research and commercial development.  Follow the tabs above to read the latest global news, research, clinical trials on stem cells and follow companies active in the stem cell industry.  BioPort...


Searches Linking to this Article