Oncotarget

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Pro-invasive properties of Snail1 are regulated by sumoylation in response to TGFβ stimulation in cancer

Shyam Kumar Gudey, Reshma Sundar, Carl-Henrik Heldin, Anders Bergh and Marene Landström _

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Oncotarget. 2017; 8:97703-97726. https://doi.org/10.18632/oncotarget.20097

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Abstract

Shyam Kumar Gudey1,*, Reshma Sundar1,*, Carl-Henrik Heldin2, Anders Bergh1 and Marene Landström1

1 Department of Medical Biosciences, Umeå University, Umeå, Sweden

2 Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Uppsala, Sweden

* These authors have contributed equally to this work

Correspondence to:

Marene Landström, email:

Keywords: signal transduction, tumor biology, Snail1, sumoylation, prostate cancer

Received: March 03, 2017 Accepted: May 19, 2017 Published: August 09, 2017

Abstract

Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT) during embryogenesis and in tumors. The effect of TGFβ, on ΕΜΤ, is conveyed by induction of the pro-invasive transcription factor Snail1. In this study, we report that TGFβ 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 TGFβ receptor I (TβRI) 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, TβRI, Hes1, and c-Jun was observed in aggressive prostate cancer tissues, consistent with their functional roles in tumorigenesis.


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