Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state
Christine L. Chaffer,Ines Brueckmann,Christina Scheel,Alicia J. Kaestli,Paul A. Wiggins,Leonardo O. Rodrigues,Mary W. Brooks,Ferenc Reinhardt,Ying Su,Kornelia Polyak,Lisa M. Arendt,Charlotte Kuperwasser,Brian Bierie,Robert A. Weinberg +13 more
TLDR
It is demonstrated that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments.Abstract:
Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectional manner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dedifferentiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconversions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer.read more
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New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer
TL;DR: It is highlighted how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state which could function as cancer stem cells, and its effects on the immunobiology of carcinomas.
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Drug Resistance in Cancer: An Overview
Genevieve Housman,Shannon Byler,Sarah Heerboth,Karolina Lapinska,Mckenna Longacre,Nicole A. Snyder,Sibaji Sarkar +6 more
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EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
TL;DR: In this paper, the authors discuss the link between the epithelial-to-mesenchymal transition (EMT) and the cancer stem cell (CSC) phenotype and discuss how this knowledge can contribute to improvements in clinical practice.
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Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells
Piyush Gupta,Christine M. Fillmore,Guozhi Jiang,Sagi Shapira,Kai Tao,Charlotte Kuperwasser,Charlotte Kuperwasser,Eric S. Lander,Eric S. Lander,Eric S. Lander +9 more
TL;DR: It is shown that subpopulations of cells purified for a given phenotypic state return towards equilibrium proportions over time, and this findings contribute to the understanding of cancer heterogeneity and reveal how stochasticity in single-cell behaviors promotes phenotypesic equilibrium in populations of cancer cells.
References
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The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
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Myeloid-derived suppressor cells as regulators of the immune system.
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Complex networks orchestrate epithelial–mesenchymal transitions
TL;DR: Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
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In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells
Gabriela Dontu,Wissam M. Abdallah,Jessica M. Foley,Kyle W. Jackson,Michael F. Clarke,Mari J. Kawamura,Max S. Wicha +6 more
TL;DR: It is demonstrated that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems.
Journal ArticleDOI
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening
Piyush Gupta,Piyush Gupta,Tamer T. Onder,Guozhi Jiang,Guozhi Jiang,Kai Tao,Charlotte Kuperwasser,Robert A. Weinberg,Eric S. Lander +8 more
TL;DR: Global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients, demonstrating the ability to identify agents with specific toxicity for epithelial CSCs.