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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Role of microRNAs in the Regulation of Breast Cancer Stem Cells
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Dynamic EpCAM expression on circulating and disseminating tumor cells: causes and consequences.
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Cancer stem cells and field cancerization of Oral squamous cell carcinoma
M. Simple,Amritha Suresh,Amritha Suresh,Debashish Das,Moni Abraham Kuriakose,Moni Abraham Kuriakose +5 more
TL;DR: If the role of CSCs as the primary units of field cancerization process is established, their presence in the mucosa adjacent to the tumor may be an indicator for local recurrence and/or development of second primary tumors.
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Epithelial-to-mesenchymal transition and cancer stem(-like) cells in head and neck squamous cell carcinoma
TL;DR: A review aims to highlight key events that are involved in EMT, discusses their relevance in HNSCC progression and metastasis and explores the possibility of targeting EMT as a novel therapy in H NSCC.
Journal ArticleDOI
Regulation of Head and Neck Squamous Cancer Stem Cells by PI3K and SOX2.
Stephen B. Keysar,Phuong Le,Bettina Miller,Brian C. Jackson,Justin R. Eagles,Cera Nieto,Jihye Kim,Binwu Tang,Magdalena J. Glogowska,John Morton,Nuria Padilla-Just,Karina A. Gómez,Emily Warnock,Julie Reisinger,John J. Arcaroli,Wells A. Messersmith,Lalage M. Wakefield,Dexiang Gao,Aik Choon Tan,Hilary S. Serracino,Vasilis Vasiliou,Dennis R. Roop,Xiao-Jing Wang,Antonio Jimeno +23 more
TL;DR: The molecular link between PI3K activation and CSC properties found in this study provides insights into therapeutic strategies for H NSCC andConstitutive expression of SOX2 in HNSCC cells generates a CSC-like population that enables CSC studies.
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Journal Article
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Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
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