MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels

Närvä, E. et al. (2022) MASTL is enriched in cancerous and pluripotent stem cells and influences OCT1/OCT4 levels. iScience, 25(6), 104459. (doi: 10.1016/j.isci.2022.104459) (PMID:35677646) (PMCID:PMC9167974)

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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.

Item Type:Articles
Additional Information:This study has been supported by the Academy of Finland (E.N. 297079 and J.I. 312517), Academy of Finland CoE for Translational Cancer Biology (J.I.), an ERC CoG grant 615258 (J.I.), InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530), the Sigrid Jusélius Foundation (J.I.), the Finnish Cancer Organization (J.I. and E.N.), Finnish Cultural Foundation (E.N., M.E.T., and A.I.) and Cancer Research UK, A17196 (S.L.) and Stand Up to Cancer campaign for Cancer Research UK A29800 (S.Z.). We also acknowledge EMBO for a short-time fellowship (E.N.).
Keywords:Cell biology, proteomics, cancer, stem cells research.
Glasgow Author(s) Enlighten ID:Lilla, Dr Sergio and Norman, Professor James and Zanivan, Professor Sara
Creator Roles:
Lilla, S.Investigation, Formal analysis, Writing – review and editing
Zanivan, S.Supervision
Norman, J.Supervision
Authors: Närvä, E., Taskinen, M. E., Lilla, S., Isomursu, A., Pietilä, M., Weltner, J., Isola, J., Sihto, H., Joensuu, H., Zanivan, S., Norman, J., and Ivaska, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:iScience
Publisher:Elsevier (Cell Press)
ISSN (Online):2589-0042
Published Online:25 May 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in iScience 25(6): 104459
Publisher Policy:Reproduced under a Creative Commons License

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