Abstract
Cancer is a complex set of diseases, driven by genomic instability overlaid with epigenetic modifications. Two prevailing concepts, the stochastic theory and the hierarchical theory, are traditionally used to understand tumor progression. These seemingly contradictory theories can be reconciled with the concept of cellular plasticity, such that certain genetic mutations enable epigenetic alterations in cell fate. A growing body of evidence suggests that cancer cells co-opt embryonic stem cell-associated regulatory networks in order to sustain tumor cell plasticity concomitant with growth and progression. The expression of these stem cell associated factors is regulated by dynamic niches, characterized by cellderived proteins as well as biophysical features such low oxygen tensions. In this review we describe specific embryoassociated proteins such as NODAL, NOTCH, and canonical WNT, which cooperate to maintain stem cell phenotypes in cancer. We also illustrate how biophysical factors, in particular oxygen, can orchestrate plasticity by modulating the expression of stem cell-associated proteins. As the microenvironment is known to play a key role in cellular regulation, it is essential to understand its role in cancer progression in order to improve and create new therapies.
Keywords: Cancer, microenvironment, NODAL, NOTCH, oxygen, plasticity, WNT
Current Stem Cell Research & Therapy
Title:Microenvironmental Regulation of Cancer Stem Cell Phenotypes
Volume: 7 Issue: 3
Author(s): Daniela F. Quail, Meghan J. Taylor and Lynne-Marie Postovit
Affiliation:
Keywords: Cancer, microenvironment, NODAL, NOTCH, oxygen, plasticity, WNT
Abstract: Cancer is a complex set of diseases, driven by genomic instability overlaid with epigenetic modifications. Two prevailing concepts, the stochastic theory and the hierarchical theory, are traditionally used to understand tumor progression. These seemingly contradictory theories can be reconciled with the concept of cellular plasticity, such that certain genetic mutations enable epigenetic alterations in cell fate. A growing body of evidence suggests that cancer cells co-opt embryonic stem cell-associated regulatory networks in order to sustain tumor cell plasticity concomitant with growth and progression. The expression of these stem cell associated factors is regulated by dynamic niches, characterized by cellderived proteins as well as biophysical features such low oxygen tensions. In this review we describe specific embryoassociated proteins such as NODAL, NOTCH, and canonical WNT, which cooperate to maintain stem cell phenotypes in cancer. We also illustrate how biophysical factors, in particular oxygen, can orchestrate plasticity by modulating the expression of stem cell-associated proteins. As the microenvironment is known to play a key role in cellular regulation, it is essential to understand its role in cancer progression in order to improve and create new therapies.
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Cite this article as:
F. Quail Daniela, J. Taylor Meghan and Postovit Lynne-Marie, Microenvironmental Regulation of Cancer Stem Cell Phenotypes, Current Stem Cell Research & Therapy 2012; 7 (3) . https://dx.doi.org/10.2174/157488812799859838
DOI https://dx.doi.org/10.2174/157488812799859838 |
Print ISSN 1574-888X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3946 |
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