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The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC

Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analy...

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Autores principales: Helweg, Laureen P., Windmöller, Beatrice A., Burghardt, Leonie, Storm, Jonathan, Förster, Christine, Wethkamp, Nils, Wilkens, Ludwig, Kaltschmidt, Barbara, Banz-Jansen, Constanze, Kaltschmidt, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910063/
https://www.ncbi.nlm.nih.gov/pubmed/35269569
http://dx.doi.org/10.3390/ijms23052426
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author Helweg, Laureen P.
Windmöller, Beatrice A.
Burghardt, Leonie
Storm, Jonathan
Förster, Christine
Wethkamp, Nils
Wilkens, Ludwig
Kaltschmidt, Barbara
Banz-Jansen, Constanze
Kaltschmidt, Christian
author_facet Helweg, Laureen P.
Windmöller, Beatrice A.
Burghardt, Leonie
Storm, Jonathan
Förster, Christine
Wethkamp, Nils
Wilkens, Ludwig
Kaltschmidt, Barbara
Banz-Jansen, Constanze
Kaltschmidt, Christian
author_sort Helweg, Laureen P.
collection PubMed
description Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analyze the molecular pathways involved in survival to identify targets for the establishment of novel therapies. Endometrial carcinoma-derived stem-like cells (ECSCs) were isolated from carcinogenic gynecological tissue and analyzed regarding their expression of prominent CSC markers. Further, they were treated with the MYC-signaling inhibitor KJ-Pyr-9, chemotherapeutic agent carboplatin and type II diabetes medication metformin. ECSC populations express common CSC markers, such as Prominin-1 and CD44 antigen as well as epithelial-to-mesenchymal transition markers, Twist, Snail and Slug, and exhibit the ability to form free-floating spheres. The inhibition of MYC signaling and treatment with carboplatin as well as metformin significantly reduced the cell survival of ECSC-like cells. Further, treatment with metformin significantly decreased the mitochondrial membrane potential of ECSC-like cells, while the extracellular lactate concentration was increased. The established ECSC-like populations represent promising in vitro models to further study the contribution of ECSCs to endometrial carcinogenesis. Targeting MYC signaling as well as mitochondrial bioenergetics has shown promising results in the diminishment of ECSCs, although molecular signaling pathways need further investigations.
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spelling pubmed-89100632022-03-11 The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC Helweg, Laureen P. Windmöller, Beatrice A. Burghardt, Leonie Storm, Jonathan Förster, Christine Wethkamp, Nils Wilkens, Ludwig Kaltschmidt, Barbara Banz-Jansen, Constanze Kaltschmidt, Christian Int J Mol Sci Article Cancer stem cells (CSCs) are a small subpopulation of tumor cells harboring properties that include self-renewal, multi-lineage differentiation, tumor reconstitution, drug resistance and invasiveness, making them key players in tumor relapse. In the present paper, we develop new CSC models and analyze the molecular pathways involved in survival to identify targets for the establishment of novel therapies. Endometrial carcinoma-derived stem-like cells (ECSCs) were isolated from carcinogenic gynecological tissue and analyzed regarding their expression of prominent CSC markers. Further, they were treated with the MYC-signaling inhibitor KJ-Pyr-9, chemotherapeutic agent carboplatin and type II diabetes medication metformin. ECSC populations express common CSC markers, such as Prominin-1 and CD44 antigen as well as epithelial-to-mesenchymal transition markers, Twist, Snail and Slug, and exhibit the ability to form free-floating spheres. The inhibition of MYC signaling and treatment with carboplatin as well as metformin significantly reduced the cell survival of ECSC-like cells. Further, treatment with metformin significantly decreased the mitochondrial membrane potential of ECSC-like cells, while the extracellular lactate concentration was increased. The established ECSC-like populations represent promising in vitro models to further study the contribution of ECSCs to endometrial carcinogenesis. Targeting MYC signaling as well as mitochondrial bioenergetics has shown promising results in the diminishment of ECSCs, although molecular signaling pathways need further investigations. MDPI 2022-02-22 /pmc/articles/PMC8910063/ /pubmed/35269569 http://dx.doi.org/10.3390/ijms23052426 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Helweg, Laureen P.
Windmöller, Beatrice A.
Burghardt, Leonie
Storm, Jonathan
Förster, Christine
Wethkamp, Nils
Wilkens, Ludwig
Kaltschmidt, Barbara
Banz-Jansen, Constanze
Kaltschmidt, Christian
The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
title The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
title_full The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
title_fullStr The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
title_full_unstemmed The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
title_short The Diminishment of Novel Endometrial Carcinoma-Derived Stem-like Cells by Targeting Mitochondrial Bioenergetics and MYC
title_sort diminishment of novel endometrial carcinoma-derived stem-like cells by targeting mitochondrial bioenergetics and myc
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910063/
https://www.ncbi.nlm.nih.gov/pubmed/35269569
http://dx.doi.org/10.3390/ijms23052426
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