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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Targeting Epithelial–Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer
Bowen Du,Joong Sup Shim +1 more
TL;DR: The mechanism by which EMT contributes to drug resistance in cancer cells is described and new advances in research in EMT-associated drug resistance are summarized.
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Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization
Virginia Tirino,Vincenzo Desiderio,Francesca Paino,Alfredo De Rosa,Federica Papaccio,Marcella La Noce,Luigi Laino,Francesco De Francesco,Gianpaolo Papaccio +8 more
TL;DR: An overview of the main characteristics and approaches used to identify, isolate, and characterize cancer stem cells from solid tumors is provided.
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Stability of the hybrid epithelial/mesenchymal phenotype
Mohit Kumar Jolly,Satyendra C. Tripathi,Dongya Jia,Steven M. Mooney,Muge Celiktas,Samir M. Hanash,Sendurai A. Mani,Kenneth J. Pienta,Eshel Ben-Jacob,Eshel Ben-Jacob,Herbert Levine +10 more
TL;DR: The results suggest that partial EMT, i.e. a hybrid E/M phenotype, need not be ‘metastable’, and strengthen the emerging notion that partialEMT, but not necessarily a complete E MT, is associated with aggressive tumor progression.
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EMT and MET: necessary or permissive for metastasis?
TL;DR: This work focuses on epithelial/mesenchymal plasticity in metastatic dissemination and proposes alternative mechanisms for successful dissemination and metastases beyond the traditional EMT/MET view.
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Biomarkers of Epithelial-Mesenchymal Transition in Squamous Cell Carcinoma
TL;DR: The findings of these studies suggest that EMT mediates H NSCC progression, and the mechanistic role of the EMT markers that have been associated with HNSCC should be more clearly defined if new anti-HNSCC therapies to block EMT progression are to be developed.
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Journal Article
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