MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels
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 pat...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222007301 |
| _version_ | 1811244500148813824 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Elisa Närvä |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T14:26:09Z |
| format | Article |
| id | doaj.art-49fc6d2d2b354fafb82f10b872696eca |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T14:26:09Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-49fc6d2d2b354fafb82f10b872696eca2022-12-22T03:29:26ZengElsevieriScience2589-00422022-06-01256104459MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levelsElisa Närvä0Maria E. Taskinen1Sergio Lilla2Aleksi Isomursu3Mika Pietilä4Jere Weltner5Jorma Isola6Harri Sihto7Heikki Joensuu8Sara Zanivan9Jim Norman10Johanna Ivaska11Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Corresponding authorTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, FinlandCRUK Beatson Institute, Glasgow G61 1BD, UKTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, FinlandTurku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, FinlandStem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki, FinlandLaboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, FinlandDepartment of Pathology, University of Helsinki, 00290 Helsinki, FinlandUniversity of Helsinki and Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, FinlandCRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UKCRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1QH, UKTurku 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222007301Cell biologyStem cells researchCancerProteomics |
| spellingShingle | 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 MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels iScience Cell biology Stem cells research Cancer Proteomics |
| title | MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels |
| title_full | MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels |
| title_fullStr | MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels |
| title_full_unstemmed | MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels |
| title_short | MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels |
| title_sort | mastl is enriched in cancerous and pluripotent stem cells and influences oct1 oct4 levels |
| topic | Cell biology Stem cells research Cancer Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222007301 |
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