Metabolic Reprograming Via Silencing of Mitochondrial VDAC1 Expression Encourages Differentiation of Cancer Cells.

08:00 EDT 18th May 2019 | BioPortfolio

Summary of "Metabolic Reprograming Via Silencing of Mitochondrial VDAC1 Expression Encourages Differentiation of Cancer Cells."

The mitochondrial gatekeeper voltage-dependent anion channel 1 (VDAC1) controls metabolic and energy cross-talk between mitochondria and the rest of the cell and is involved in mitochondria-mediated apoptosis. Here, we compared the effects of downregulated VDAC1 expression in the U-87MG glioblastoma, MDA-MB-231 triple-negative breast cancer (TNBC), and A549 lung cancer cell lines, using small interfering RNA (siRNA) specific to human VDAC1 (si-hVDAC1). The cells were subjected to si-hVDAC1 (50 nM) treatment for 5-20 days. Although VDAC1 silencing occurred within a day, the cells underwent reprograming with respect to rewiring metabolism, elimination of cancer stem cells (CSCs), and alteration of transcription factor (TF) expression and proteins associated with differentiation, with maximal changes being observed after 3 weeks of silencing VDAC1 expression. The differentiation into fewer tumorigenic cells may be associated with the elimination of CSCs. These alterations are interconnected, as protein up- or downregulation occurred simultaneously, starting 15-20 days after VDAC1 levels were first decreased. Moreover, the VDAC1 depletion-mediated effects on a network of key regulators of cell metabolism, CSCs, TFs, and other factors leading to differentiation are coordinated and are common to the glioblastoma multiforme (GBM) and lung and breast cancer cell lines, despite differing in origin and carried mutations. Thus, our study showed that VDAC1 depletion triggers reprograming of malignant cancer cells into terminally differentiated cells and that this may be a promising therapeutic approach for various cancers.


Journal Details

This article was published in the following journal.

Name: Molecular therapy. Nucleic acids
ISSN: 2162-2531
Pages: 24-37


DeepDyve research library

PubMed Articles [18903 Associated PubMed Articles listed on BioPortfolio]

The mitochondrial retrograde signaling regulates Wnt signaling to promote tumorigenesis in colon cancer.

Cancer cells are known to upregulate aerobic glycolysis to promote growth, proliferation, and survival. However, the role of mitochondrial respiration in tumorigenesis remains elusive. Here we report ...

HSP60 silencing promotes Warburg-like phenotypes and switches the mitochondrial function from ATP production to biosynthesis in ccRCC cells.

HSP60 is a major mitochondrial chaperone for maintaining mitochondrial proteostasis. Our previous studies showed that HSP60 was significantly downregulated in clear cell renal cell carcinoma (ccRCC), ...

Antigen receptor control of methionine metabolism in T cells.

Immune activated T lymphocytes modulate the activity of key metabolic pathways to support the transcriptional reprograming and reshaping of cell proteomes that permits effector T cell differentiation....

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 ...

PINK1/parkin-mediated mitophagy pathway is related to neuroprotection by carnosic acid in SH-SY5Y cells.

Impairment in mitophagy contributes to the pathology of Parkinson's disease. This study investigated whether Phosphatase and tensin homologue (PTEN)-induced kinase 1 (PINK1)/parkin-mediated mitophagy ...

Clinical Trials [4878 Associated Clinical Trials listed on BioPortfolio]

GDF-15 as a Biomarker for Mitochondrial Disease

Mitochondrial disorders are a group of inherited disorders causing malfunctional mitochondria. Mitochondria are found in every cell of the body, and the disorders therefore give symptoms f...

Time-course of Mitochondrial Biogenic Gene and Protein Expression in Exercised Human Skeletal Muscle

This study examines the impact of exercise intensity on the 12-hour time-course of mitochondrial biogenic gene and protein expression in human skeletal muscle. Briefly, participants will p...

In and ex Vivo Mitochondrial Function of the Heart

It has been suggested that mitochondrial dysfunction might play a role in the development of diabetic cardiomyopathy. From animal studies, it has been suggested that an altered PPAR and PG...

mtDNA and Embryo Metabolism

The present study has the objective to study whether the mitochondrial DNA copy number values that can be generated when human embryos are analyzed for chromosomal content before embryo tr...

Trial of Oral Glutamine on Mitochondrial Function in CKD

The primary goal of proposed investigation is to study the impact of oral glutamine supplementation on muscle mitochondrial and endothelial cell function measured mitochondrial energetics ...

Medical and Biotech [MESH] Definitions

Interruption or suppression of the expression of a gene at transcriptional or translational levels.

A mitochondrial uncoupling protein that is expressed in many tissues and exhibits the greatest expression in SKELETAL MUSCLE. It regulates mitochondrial ATP production and the generation of REACTIVE OXYGEN SPECIES.

A transcriptional co-activator for NUCLEAR RECEPTORS. It is characterized by an N-terminal LxxLL sequence, a region that interacts with PPAR GAMMA, and a C-terminal RNA RECOGNITION MOTIF. It increases expression of MITOCHONDRIAL UNCOUPLING PROTEIN to regulate genes involved in metabolic reprogramming in response to dietary restriction and the integration of CIRCADIAN RHYTHMS with ENERGY METABOLISM.

A winged-helix transcription factor that regulates GENE expression in metabolic tissues. It plays a role in HOMEOSTASIS of GLUCOSE and controls expression of GLUT2 PROTEIN.

The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.

Quick Search


DeepDyve research library

Relevant Topic

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

Searches Linking to this Article