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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The receptor tyrosine kinase Axl regulates cell-cell adhesion and stemness in cutaneous squamous cell carcinoma.
Monika A. Cichoń,Z Szentpetery,M. Caley,E S Papadakis,Ian C. Mackenzie,Caroline H. Brennan,Edel A. O'Toole +6 more
TL;DR: It is suggested that abrogation of Axl results in loss of cancer stem cell properties indicating a role for Axl as a therapeutic target in chemotherapy-resistant cancer.
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Implications of stemness-related signaling pathways in breast cancer response to therapy
TL;DR: Efforts to develop alternative BCIC-targeted therapies against stemness markers (CD44 and ALDH1) and molecules involved in regulating EMT- and HER2-related pathways, or able to reverse the multi-drug resistance phenotype, or to induce differentiation and to control cell survival pathways are currently ongoing.
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HIF-1α induces the epithelial-mesenchymal transition in gastric cancer stem cells through the Snail pathway.
Yang Shiwei,Zhi-gang Zhang,Yingxue Hao,Yong-liang Zhao,Feng Qian,Yan Shi,Pingang Li,Chunyang Liu,Peiwu Yu +8 more
TL;DR: The results demonstrated that hypoxia-induced EMT-like CSCs rely on HIF-1α to activate Snail, which may result in recurrence and metastasis of gastric cancer.
Journal ArticleDOI
Notch1-MAPK Signaling Axis Regulates CD133+ Cancer Stem Cell-Mediated Melanoma Growth and Angiogenesis.
Dhiraj Kumar,Santosh Kumar,Mahadeo Gorain,Deepti Tomar,Harshal S. Patil,N. N. V. Radharani,Totakura V. S. Kumar,Tushar Patil,Hirekodathakallu V. Thulasiram,Gopal C. Kundu +9 more
TL;DR: It is reported that melanoma-specific CD133+ cancer stem cells exhibit increased tumor-initiating potential, tumor-endothelial cell interaction, and lung metastasis, and Notch1 intracellular domain regulates CD133 expression at the transcriptional level.
Journal ArticleDOI
Identification of a Population of Epidermal Squamous Cell Carcinoma Cells with Enhanced Potential for Tumor Formation
Gautam Adhikary,Dan Grun,Candace L. Kerr,Sivaprakasam Balasubramanian,Ellen A. Rorke,Mohan C. Vemuri,Shayne Boucher,Jackie R. Bickenbach,Thomas J. Hornyak,Wen Xu,Matthew L. Fisher,Richard L. Eckert +11 more
TL;DR: It is indicated that a subpopulation of cells that possess stem cell-like properties and express stem cell markers can be derived from human epidermal cancer cells and that these cells display enhanced ability to drive tumor formation.
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Journal Article
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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).