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JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma
Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy‐resistant cells in MLS remains unknow...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590236/ https://www.ncbi.nlm.nih.gov/pubmed/30650179 http://dx.doi.org/10.1002/ijc.32123 |
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author | Dolatabadi, Soheila Jonasson, Emma Lindén, Malin Fereydouni, Bentolhoda Bäcksten, Karin Nilsson, Malin Martner, Anna Forootan, Amin Fagman, Henrik Landberg, Göran Åman, Pierre Ståhlberg, Anders |
author_facet | Dolatabadi, Soheila Jonasson, Emma Lindén, Malin Fereydouni, Bentolhoda Bäcksten, Karin Nilsson, Malin Martner, Anna Forootan, Amin Fagman, Henrik Landberg, Göran Åman, Pierre Ståhlberg, Anders |
author_sort | Dolatabadi, Soheila |
collection | PubMed |
description | Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy‐resistant cells in MLS remains unknown. Here, we show that MLS cell lines contained subpopulations of cells that can form spheres, efflux Hoechst dye and resist doxorubicin, all properties attributed to cancer stem cells (CSCs). By single‐cell gene expression, western blot, phospho‐kinase array, immunoprecipitation, immunohistochemistry, flow cytometry and microarray analysis we showed that a subset of MLS cells expressed JAK–STAT genes with active signalling. JAK1/2 inhibition via ruxolitinib decreased, while stimulation with LIF increased, phosphorylation of STAT3 and the number of cells with CSC properties indicating that JAK–STAT signalling controlled the number of cells with CSC features. We also show that phosphorylated STAT3 interacted with the SWI/SNF complex. We conclude that MLS contains JAK–STAT‐regulated subpopulations of cells with CSC features. Combined doxorubicin and ruxolitinib treatment targeted both proliferating cells as well as cells with CSC features, providing new means to circumvent chemotherapy resistance in treatment of MLS patients. |
format | Online Article Text |
id | pubmed-6590236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65902362019-07-08 JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma Dolatabadi, Soheila Jonasson, Emma Lindén, Malin Fereydouni, Bentolhoda Bäcksten, Karin Nilsson, Malin Martner, Anna Forootan, Amin Fagman, Henrik Landberg, Göran Åman, Pierre Ståhlberg, Anders Int J Cancer Molecular Cancer Biology Myxoid liposarcoma (MLS) shows extensive intratumoural heterogeneity with distinct subpopulations of tumour cells. Despite improved survival of MLS patients, existing therapies have shortcomings as they fail to target all tumour cells. The nature of chemotherapy‐resistant cells in MLS remains unknown. Here, we show that MLS cell lines contained subpopulations of cells that can form spheres, efflux Hoechst dye and resist doxorubicin, all properties attributed to cancer stem cells (CSCs). By single‐cell gene expression, western blot, phospho‐kinase array, immunoprecipitation, immunohistochemistry, flow cytometry and microarray analysis we showed that a subset of MLS cells expressed JAK–STAT genes with active signalling. JAK1/2 inhibition via ruxolitinib decreased, while stimulation with LIF increased, phosphorylation of STAT3 and the number of cells with CSC properties indicating that JAK–STAT signalling controlled the number of cells with CSC features. We also show that phosphorylated STAT3 interacted with the SWI/SNF complex. We conclude that MLS contains JAK–STAT‐regulated subpopulations of cells with CSC features. Combined doxorubicin and ruxolitinib treatment targeted both proliferating cells as well as cells with CSC features, providing new means to circumvent chemotherapy resistance in treatment of MLS patients. John Wiley & Sons, Inc. 2019-01-29 2019-07-15 /pmc/articles/PMC6590236/ /pubmed/30650179 http://dx.doi.org/10.1002/ijc.32123 Text en © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Molecular Cancer Biology Dolatabadi, Soheila Jonasson, Emma Lindén, Malin Fereydouni, Bentolhoda Bäcksten, Karin Nilsson, Malin Martner, Anna Forootan, Amin Fagman, Henrik Landberg, Göran Åman, Pierre Ståhlberg, Anders JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
title | JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
title_full | JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
title_fullStr | JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
title_full_unstemmed | JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
title_short | JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
title_sort | jak–stat signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma |
topic | Molecular Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590236/ https://www.ncbi.nlm.nih.gov/pubmed/30650179 http://dx.doi.org/10.1002/ijc.32123 |
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