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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Epithelial Plasticity, Autophagy and Metastasis: Potential Modifiers of the Crosstalk to Overcome Therapeutic Resistance.
TL;DR: Combinational treatments based on targeting autophagic CSCs and inhibiting EMT regulators may represent potential anticancer strategies for the prevention of cancer invasion, metastatic spread and disease relapse.
Journal ArticleDOI
Epithelial-Mesenchymal Transition Associated with Head and Neck Squamous Cell Carcinomas: A Review.
Rogelio González-González,Gamaliel Ortiz-Sarabia,Nelly Molina-Frechero,José M. Salas-Pacheco,Sergio Manuel Salas-Pacheco,Jesús Lavalle-Carrasco,Sandra López-Verdín,Omar Tremillo-Maldonado,Ronell Bologna-Molina,Ronell Bologna-Molina +9 more
TL;DR: In this article, the main molecules related to EMT, their interactions with the tumor microenvironment, plasticity phenomena, epigenetic regulation, hypoxia, inflammation, their relationship with immune cells, and the inhibition of EMT in the context of head and neck squamous cell carcinomas (HNSCCs) are discussed.
Journal ArticleDOI
3D spheroid models of paediatric SHH medulloblastoma mimic tumour biology, drug response and metastatic dissemination.
TL;DR: In this article, a robust, reliable, three-dimensional (3D) culture method for medulloblastoma able to recapitulate the spatial conformation, cell-cell and cell-matrix interactions that exist in vivo and in patient tumours was proposed.
Journal ArticleDOI
Surgical margins in the genomic era: The Hayes Martin Lecture, 2012.
TL;DR: A futuristic and somewhat theoretical view of how surgical margin issues will relate to the personalization of modern head and neck cancer treatment and how the biology of the tumor microenvironment may be instructive in the application of the authors' surgical approaches is provided.
Journal ArticleDOI
Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem.
Jacob M. Smigiel,Sarah E. Taylor,Benjamin L. Bryson,Ilaria Tamagno,Kelsey Polak,Mark W. Jackson +5 more
TL;DR: The importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor and how one may potentially target these populations is discussed, ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.
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Journal Article
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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
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Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
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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).