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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HMGA2 regulates epithelial-mesenchymal transition and the acquisition of tumor stem cell properties through TWIST1 in gastric cancer
TL;DR: HMGA2 regulates the EMT of gastric cancer cells and the acquisition of tumor stem cell properties through direct regulation of the downstream target gene TWIST1.
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miR‑181b‑5p mediates TGF‑β1-induced epithelial-to-mesenchymal transition in non-small cell lung cancer stem-like cells derived from lung adenocarcinoma A549 cells
TL;DR: It is suggested that miR-181b-5p regulates TGF-β1-induced EMT by targeting E-cadherin not only in normal A549 cells but also in CD133+/CD326+ cells which have characteristics of CSLCs.
Journal ArticleDOI
Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification
Martin Leinung,Benjamin Philipp Ernst,Constanze Döring,Jens Wagenblast,Aykut Tahtali,Marc Diensthuber,Timo Stöver,Christin Geissler +7 more
TL;DR: CD44 appeared to interact with EGFR and was more often expressed in primary HNSCC than the marker ALDH1A1, however, ALDH2A1 was a better marker to define a subpopulation of tumor cells and was sufficient to determine the CSC population in H NSCC.
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Na+/K+-ATPase β2-subunit (AMOG) expression abrogates invasion of glioblastoma-derived brain tumor-initiating cells
Matthew Z. Sun,Joseph M. Kim,Michael C. Oh,Michael Safaee,Gurvinder Kaur,Aaron J. Clark,Orin Bloch,Michael E. Ivan,Rajwant Kaur,Taemin Oh,Shaun D. Fouse,Joanna J. Phillips,Mitchel S. Berger,Andrew T. Parsa +13 more
TL;DR: Overexpression of AMOG decreased GBM cell and BTIC invasion without affecting migration or proliferation, and its downregulation increases invasion in glial cells and may also represent an important step in BTIC differentiation.
Journal ArticleDOI
The expression of aldehyde dehydrogenase 1 (ALDH1) in ovarian carcinomas and its clinicopathological associations: a retrospective study
Ruixia Huang,Ruixia Huang,Xiaoran Li,Xiaoran Li,Ruth Holm,Claes G. Tropé,Claes G. Tropé,Jahn M. Nesland,Jahn M. Nesland,Zhenhe Suo,Zhenhe Suo +10 more
TL;DR: High expression of cancer stem cell marker ALDH1 in ovarian carcinoma cells may portend a favorable prognosis, but its expression in tumor microenvironment may have no role in tumor behavior of ovarian carcinomas.
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Journal Article
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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
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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).