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JAK–STAT signalling...
JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma
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- Dolatabadi, Soheila (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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- Jonasson, Emma, 1987 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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- Lindén, Malin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Cancer Center,Department of Laboratory Medicine
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- Fereydouni, Bentolhoda (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Cancer Center,Department of Laboratory Medicine
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- Bäcksten, Karin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Cancer Center,Department of Laboratory Medicine
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- Nilsson, Malin (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Martner, Anna, 1979 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center
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- Forootan, Amin (author)
- Gothenburg University,Göteborgs universitet,Extern,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för laboratoriemedicin,External,Department of Laboratory Medicine
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- Fagman, Henrik, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Cancer Center,Extern,Department of Laboratory Medicine,External
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- Landberg, Göran, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Cancer Center,Department of Laboratory Medicine
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- Åman, Pierre, 1953 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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- Ståhlberg, Anders, 1975 (author)
- Gothenburg University,Göteborgs universitet,Extern,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Cancer Center,Institutionen för biomedicin, avdelningen för laboratoriemedicin,External,Department of Laboratory Medicine
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(creator_code:org_t)
- 2019-01-29
- 2019
- English.
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:2, s. 435-449
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Abstract
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- 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. © 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- cancer stem cells
- chemotherapy resistance
- JAK–STAT signalling
- LIF
- myxoid liposarcoma
- ruxolitinib
- SWI/SNF
Publication and Content Type
- ref (subject category)
- art (subject category)
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Dolatabadi, Sohe ...
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Jonasson, Emma, ...
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Lindén, Malin
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Fereydouni, Bent ...
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Bäcksten, Karin
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Nilsson, Malin
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Martner, Anna, 1 ...
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Forootan, Amin
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Fagman, Henrik, ...
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Landberg, Göran, ...
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Åman, Pierre, 19 ...
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Ståhlberg, Ander ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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University of Gothenburg