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Pro-invasive properties of Snail1 are regulated by sumoylation in response to TGFβ stimulation in cancer
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 58, p. 97703-97726Article in journal (Refereed) Published
Abstract [en]

Transforming growth factor beta (TGF beta) is a key regulator of epithelial-tomesenchymal transition (EMT) during embryogenesis and in tumors. The effect of TGF beta, on EMT, is conveyed by induction of the pro-invasive transcription factor Snail1. In this study, we report that TGF beta stimulates Snail1 sumoylation in aggressive prostate, breast and lung cancer cells. Sumoylation of Snail1 lysine residue 234 confers its transcriptional activity, inducing the expression of classical EMT genes, as well as TGF beta receptor I (T beta RI) and the transcriptional repressor Hes1. Mutation of Snail1 lysine residue 234 to arginine (K234R) abolished sumoylation of Snail1, as well as its migratory and invasive properties in human prostate cancer cells. An increased immunohistochemical expression of Snail1, Sumo1, T beta RI, Hes1, and c-Jun was observed in aggressive prostate cancer tissues, consistent with their functional roles in tumorigenesis.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2017. Vol. 8, no 58, p. 97703-97726
Keywords [en]
signal transduction, tumor biology, Snail1, sumoylation, prostate cancer
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-144979DOI: 10.18632/oncotarget.20097ISI: 000419392300002PubMedID: 29228645OAI: oai:DiVA.org:umu-144979DiVA, id: diva2:1184226
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2019-05-09Bibliographically approved

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Gudey, Shyam KumarSundar, ReshmaBergh, AndersLandström, Marene

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