Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative
Adrian Biddle,Xiao Liang,Luke Gammon,Bilal Fazil,Lisa J. Harper,Helena Emich,Daniela Elena Costea,Ian C. Mackenzie +7 more
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TLDR
A need to define therapeutic targets that can eradicate both EMT and self-renewing CSC variants to achieve effective SCC treatment is suggested.Abstract:
Epithelial-to-mesenchymal transition (EMT) is an important driver of tumor invasion and metastasis, which causes many cancer deaths. Cancer stem cells (CSC) that maintain and initiate tumors have also been implicated in invasion and metastasis, but whether EMT is an important contributor to CSC function is unclear. In this study, we investigated whether a population of CSCs that have undergone EMT (EMT CSCs) exists in squamous cell carcinoma (SCC). We also determined whether a separate population of CSCs that retain epithelial characteristics (non-EMT CSCs) is also present. Our studies revealed that self-renewing CSCs in SCC include two biologically-distinct phenotypes. One phenotype, termed CD44(high)ESA(high), was proliferative and retained epithelial characteristics (non-EMT CSCs), whereas the other phenotype, termed CD44(high)ESA(low), was migratory and had mesenchymal traits characteristic of EMT CSCs. We found that non-EMT and EMT CSCs could switch their epithelial or mesenchymal traits to reconstitute the cellular heterogeneity which was characteristic of CSCs. However, the ability of EMT CSCs to switch to non-EMT character was restricted to cells that were also ALDH1(+), implying that only ALDH1(+) EMT cells had the ability to seed a new epithelial tumor. Taken together, our findings highlight the identification of two distinct CSC phenotypes and suggest a need to define therapeutic targets that can eradicate both of these variants to achieve effective SCC treatment.read more
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Expression of PIWIL2 in oral cancer and leukoplakia: Prognostic implications and insights from tumors.
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References
More filters
Journal ArticleDOI
Prospective identification of tumorigenic breast cancer cells
Muhammad Al-Hajj,Max S. Wicha,Adalberto Benito-Hernandez,Sean J. Morrison,Sean J. Morrison,Michael F. Clarke +5 more
TL;DR: The ability to prospectively identify tumorigenic cancer cells will facilitate the elucidation of pathways that regulate their growth and survival and strategies designed to target this population may lead to more effective therapies.
Journal ArticleDOI
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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Identification of a Cancer Stem Cell in Human Brain Tumors
Sheila K. Singh,Ian D. Clarke,Mizuhiko Terasaki,Victoria E. Bonn,Cynthia Hawkins,Jeremy A. Squire,Peter B. Dirks +6 more
TL;DR: The identification and purification of a cancer stem cell from human brain tumors of different phenotypes that possesses a marked capacity for proliferation, self-renewal, and differentiation is reported.
Journal ArticleDOI
ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
Christophe Ginestier,Min Hee Hur,Emmanuelle Charafe-Jauffret,Florence Monville,Julie Dutcher,Marty Brown,Jocelyne Jacquemier,Patrice Viens,Celina G. Kleer,Suling Liu,Anne F. Schott,Daniel F. Hayes,Daniel Birnbaum,Max S. Wicha,Gabriela Dontu +14 more
TL;DR: It is shown that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties and these cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
Journal ArticleDOI
Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Jing Yang,Sendurai A. Mani,Joana Liu Donaher,Sridhar Ramaswamy,Sridhar Ramaswamy,Raphael Itzykson,Christophe Côme,Pierre Savagner,Inna Gitelman,Andrea L. Richardson,Robert A. Weinberg +10 more
TL;DR: A mechanistic link between Twist, EMT, and tumor metastasis is established, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT).