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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Esophageal Adenocarcinoma Cells and Xenograft Tumors Exposed to Erb-b2 Receptor Tyrosine Kinase 2 and 3 Inhibitors Activate Transforming Growth Factor Beta Signaling, Which Induces Epithelial to Mesenchymal Transition
Eva A. Ebbing,Anne Steins,Evelyn Fessler,Phylicia Stathi,Willem Joost Lesterhuis,Kausilia K. Krishnadath,Louis Vermeulen,Jan Paul Medema,Maarten F. Bijlsma,Hanneke W. M. van Laarhoven +9 more
TL;DR: Mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft tumors to ERBB inhibitors are investigated and high expression of ERBB3 is associated with an epithelial to mesenchymal transition (EMT) gene expression signature; expression of TGFβ correlated with expression of EMT-related genes, and an inverse correlation between expression ofTGFB1 and ER BB3 is found.
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Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma.
Maria Fernanda Setúbal Destro Rodrigues,Luke Gammon,Muhammad M Rahman,Adrian Biddle,Fábio Daumas Nunes,Ian C. Mackenzie +5 more
TL;DR: EGFR blocking induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.
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Biological role of metabolic reprogramming of cancer cells during epithelial‑mesenchymal transition (Review)
TL;DR: A basis for treatments targeting the tumor EMT process and metabolic reprogramming is provided and some findings have resulted in novel clinical applications.
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CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma.
Rafael Carneiro Ortiz,Nathália Martins Lopes,Nádia Ghinelli Amôr,José Burgos Ponce,Claudia Kliemann Schmerling,Vanessa Soares Lara,Raquel Ajub Moyses,Camila Oliveira Rodini +7 more
TL;DR: It is suggested that immunoexpression of CD44 and ALDH1 links the cancer stem cell phenotype with oral squamous cell carcinoma invasion and metastasis.
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CTC phenotyping for a preoperative assessment of tumor metastasis and overall survival of pancreatic ductal adenocarcinoma patients.
Yukun Sun,Guangdong Wu,Guangdong Wu,Kok Suen Cheng,Anqi Chen,Kuang Hong Neoh,Shuiyu Chen,Zhewen Tang,Poh Foong Lee,Menghua Dai,Ray P. S. Han,Ray P. S. Han +11 more
TL;DR: The CTC phenotyping model has the potential to be developed into a reliable and accurate blood test for metastatic and OS assessments of PDAC patients and is suggested to be a significant independent predictor of OS.
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