MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels
Elisa Närvä,
Maria E. Taskinen,
Sergio Lilla,
Aleksi Isomursu,
Mika Pietilä,
Jere Weltner,
Jorma Isola,
Harri Sihto,
Heikki Joensuu,
Sara Zanivan,
Jim Norman,
Johanna Ivaska
Affiliations
Elisa Närvä
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Corresponding author
Maria E. Taskinen
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Sergio Lilla
CRUK Beatson Institute, Glasgow G61 1BD, UK
Aleksi Isomursu
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Mika Pietilä
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland
Jere Weltner
Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland
Jorma Isola
Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland
Harri Sihto
Department of Pathology, University of Helsinki, 00290 Helsinki, Finland
Heikki Joensuu
University of Helsinki and Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, Finland
Sara Zanivan
CRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
Jim Norman
CRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UK
Johanna Ivaska
Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Department of Life Technologies, University of Turku, 20520 Turku, Finland; Western Finnish Cancer Center (FICAN West), University of Turku, 20520 Turku, Finland; Foundation for the Finnish Cancer Institute, Tukholmankatu 8, Helsinki, Finland; Corresponding author
Summary: MASTL is a mitotic accelerator with an emerging role in breast cancer progression. However, the mechanisms behind its oncogenicity remain largely unknown. Here, we identify a previously unknown role and eminent expression of MASTL in stem cells. MASTL staining from a large breast cancer patient cohort indicated a significant association with β3 integrin, an established mediator of breast cancer stemness. MASTL silencing reduced OCT4 levels in human pluripotent stem cells and OCT1 in breast cancer cells. Analysis of the cell-surface proteome indicated a strong link between MASTL and the regulation of TGF-β receptor II (TGFBR2), a key modulator of TGF-β signaling. Overexpression of wild-type and kinase-dead MASTL in normal mammary epithelial cells elevated TGFBR2 levels. Conversely, MASTL depletion in breast cancer cells attenuated TGFBR2 levels and downstream signaling through SMAD3 and AKT pathways. Taken together, these results indicate that MASTL supports stemness regulators in pluripotent and cancerous stem cells.
