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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Somatic to iPS Cell Reprogramming

Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012 for this...
Methods of Nuclear Reprogramming01:24

Methods of Nuclear Reprogramming

Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for injury repair.
Introduction to Nuclear Reprogramming01:14

Introduction to Nuclear Reprogramming

Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
Metastasis02:30

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Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
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Published on: April 7, 2017

Epigenetically reprogramming metastatic tumor cells with an embryonic microenvironment.

Fabricio F Costa1, Elisabeth A Seftor, Jared M Bischof

  • 1Cancer Biology and Epigenomics Program, Children’s Memorial Research Center and Northwestern University’s Feinberg School of Medicine, 2300 Children’s Plaza, Chicago, IL 60614, USA. mjchendrix@childrensmemorial.org

Epigenomics
|May 25, 2010
PubMed
Summary

Human embryonic stem cell microenvironments reprogram aggressive cancer cells. Epigenetic changes, including microRNA regulation and DNA methylation, are key mechanisms driving these tumor cell plasticity and metastatic phenotype alterations.

Keywords:
DNA methylationLeftyNodalNotchhESC microenvironmentmicroRNAs

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Area of Science:

  • Cancer biology
  • Stem cell biology
  • Epigenetics

Background:

  • Human embryonic stem cell (hESC) microenvironments can reprogram aggressive cancer cells into a less aggressive state.
  • The Nodal signaling pathway is implicated in cancer cell plasticity, but other molecular mechanisms like microRNA (miRNA) regulation and DNA methylation may also be involved.

Purpose of the Study:

  • To investigate the epigenetic mechanisms, specifically miRNA regulation and DNA methylation, underlying phenotypic changes in metastatic melanoma cells exposed to an hESC microenvironment.

Main Methods:

  • Screened 365 miRNAs using TaqMan® Low Density Arrays.
  • Assessed DNA methylation's role in regulating Lefty expression (an inhibitor of Nodal) in hESCs versus melanoma cells.

Main Results:

  • Identified specific miRNAs (e.g., miR-302a, miR-27b) that are up- and down-regulated in melanoma cells after hESC microenvironment exposure.
  • Demonstrated Notch4 as a target of miR-302a, upstream of Nodal.
  • Provided evidence that DNA methylation may silence Lefty expression in cancer cells, contributing to unregulated Nodal expression.

Conclusions:

  • Epigenetic modifications, including DNA methylation and miRNA regulation, are significant factors in tumor cell plasticity and the metastatic phenotype.
  • These findings offer new insights into the molecular mechanisms underlying cancer reprogramming by stem cell microenvironments.