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Epigenetics and Cancer Stem Cells: Unleashing, Hijacking, and Restricting Cellular Plasticity.

ABSTRACT: Epigenetic mechanisms have emerged as key players in cancer development which affect cellular states at multiple stages of the disease. During carcinogenesis, alterations in chromatin and DNA methylation resulting from genetic lesions unleash cellular plasticity and favor oncogenic cellular reprogramming. At later stages, during cancer growth and progression, additional epigenetic changes triggered by interaction with the microenvironment modulate cancer cell phenotypes and properties, and shape tumor architecture. We review here recent advances highlighting the interplay between epigenetics, genetics, and cell-to-cell signaling in cancer, with particular emphasis on mechanisms relevant for cancer stem cell formation (CSC) and function.

SUBMITTER: Wainwright EN

PROVIDER: S-EPMC5506260 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Epigenetics and Cancer Stem Cells: Unleashing, Hijacking, and Restricting Cellular Plasticity.

Wainwright Elanor N EN Scaffidi Paola P

Trends in cancer 20170505 5

Epigenetic mechanisms have emerged as key players in cancer development which affect cellular states at multiple stages of the disease. During carcinogenesis, alterations in chromatin and DNA methylation resulting from genetic lesions unleash cellular plasticity and favor oncogenic cellular reprogramming. At later stages, during cancer growth and progression, additional epigenetic changes triggered by interaction with the microenvironment modulate cancer cell phenotypes and properties, and shape ...[more]

PMID: 28718414

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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

Epigenetics and Cancer Stem Cells: Unleashing, Hijacking, and Restricting Cellular Plasticity.

Publications

Epigenetics and Cancer Stem Cells: Unleashing, Hijacking, and Restricting Cellular Plasticity.

Similar Datasets

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