Premium
JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma
Author(s) -
Dolatabadi Soheila,
Jonasson Emma,
Lindén Malin,
Fereydouni Bentolhoda,
Bäcksten Karin,
Nilsson Malin,
Martner Anna,
Forootan Amin,
Fagman Henrik,
Landberg Göran,
Åman Pierre,
Ståhlberg Anders
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32123
Subject(s) - cancer research , biology , myxoid liposarcoma , ruxolitinib , stem cell , stem cell marker , cancer stem cell , stat3 , janus kinase , flow cytometry , jak stat signaling pathway , signal transduction , pathology , immunology , medicine , microbiology and biotechnology , tyrosine kinase , liposarcoma , sarcoma , myelofibrosis , bone marrow
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.