Dataset Information

Metabolic Targeting of Cancer Stem Cells.

ABSTRACT: Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor-regenerating and tumor-propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell population. Reprogramming of CSC metabolic pathways plays an essential role in tumor progression and metastatic spread. Many of these pathways confer cell adaptation to the microenvironmental stresses, including a shortage of nutrients and anti-cancer therapies. A better understanding of CSC metabolic dependences as well as metabolic communication between CSCs and the tumor microenvironment are of utmost importance for efficient cancer treatment. In this mini-review, we discuss the general characteristics of CSC metabolism and potential metabolic targeting of CSC populations as a potent strategy to enhance the efficacy of conventional treatment approaches.

SUBMITTER: Mukha A

PROVIDER: S-EPMC7783393 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolic Targeting of Cancer Stem Cells.

Mukha Anna A Dubrovska Anna A

Frontiers in oncology 20201222

Most human tumors possess a high heterogeneity resulting from both clonal evolution and cell differentiation program. The process of cell differentiation is initiated from a population of cancer stem cells (CSCs), which are enriched in tumor-regenerating and tumor-propagating activities and responsible for tumor maintenance and regrowth after treatment. Intrinsic resistance to conventional therapies, as well as a high degree of phenotypic plasticity, makes CSCs hard-to-target tumor cell populati ...[more]

PMID: 33415069

Similar Datasets

Project description:Ovarian Cancer is the fifth most common cancer in females and remains the most lethal gynecological malignancy as most patients are diagnosed at late stages of the disease. Despite initial responses to therapy, recurrence of chemo-resistant disease is common. The presence of residual cancer stem cells (CSCs) with the unique ability to adapt to several metabolic and signaling pathways represents a major challenge in developing novel targeted therapies. The objective of this study is to investigate the transcripts of putative ovarian cancer stem cell (OCSC) markers in correlation with transcripts of receptors, transporters, and enzymes of the energy generating metabolic pathways involved in high grade serous ovarian cancer (HGSOC). We conducted correlative analysis in data downloaded from The Cancer Genome Atlas (TCGA), studies of experimental OCSCs and their parental lines from Gene Expression Omnibus (GEO), and Cancer Cell Line Encyclopedia (CCLE). We found positive correlations between the transcripts of OCSC markers, specifically CD44, and glycolytic markers. TCGA datasets revealed that NOTCH1, CD133, CD44, CD24, and ALDH1A1, positively and significantly correlated with tricarboxylic acid cycle (TCA) enzymes. OVCAR3-OCSCs (cancer stem cells derived from a well-established epithelial ovarian cancer cell line) exhibited enrichment of the electron transport chain (ETC) mainly in complexes I, III, IV, and V, further supporting reliance on the oxidative phosphorylation (OXPHOS) phenotype. OVCAR3-OCSCs also exhibited significant increase in CD36, ACACA, SCD, and CPT1A, with CD44, CD133, and ALDH1A1 exhibiting positive correlations with lipid metabolic enzymes. TCGA data show positive correlations between OCSC markers and glutamine metabolism enzymes, whereas in OCSC experimental models of GSE64999, GSE28799, and CCLE, the number of positive and negative correlations observed was significantly lower and was different between model systems. Appropriate integration and validation of data model systems with those in patients' specimens is needed not only to bridge our knowledge gap of metabolic programing of OCSCs, but also in designing novel strategies to target the metabolic plasticity of dormant, resistant, and CSCs.

Dataset Information

Metabolic Targeting of Cancer Stem Cells.

Publications

Metabolic Targeting of Cancer Stem Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets