2. Academic Validation
  3. SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth

SMYD2 targets RIPK1 and restricts TNF-induced apoptosis and necroptosis to support colon tumor growth

  • Cell Death Dis. 2022 Jan 12;13(1):52. doi: 10.1038/s41419-021-04483-0.
Yu-Qiang Yu 1 2,  Veronika Thonn 1 2,  Jay V Patankar 1 2,  Oana-Maria Thoma 1 2,  Maximilian Waldner 1 2,  Marta Zielinska 1 3,  Li-Li Bao 1 2,  Miguel Gonzalez-Acera 1 2,  Stefan Wallmüller 1 2,  Felix B Engel 4 5,  Michael Stürzl 6,  Markus F Neurath 1 2,  Eva Liebing 1 2,  Christoph Becker 7 8
Affiliations

Affiliations

  • 1 Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • 2 Deutsches Zentrum Immuntherapie (DZI), 91054, Erlangen, Germany.
  • 3 Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland.
  • 4 Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
  • 5 Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054, Erlangen, Germany.
  • 6 Division of Molecular and Experimental Surgery, Department of Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
  • 7 Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. christoph.becker@uk-erlangen.de.
  • 8 Deutsches Zentrum Immuntherapie (DZI), 91054, Erlangen, Germany. christoph.becker@uk-erlangen.de.
PMID: 35022391 DOI: 10.1038/s41419-021-04483-0
Abstract

SMYD2 is a Histone Methyltransferase, which methylates both histone H3K4 as well as a number of non-histone proteins. Dysregulation of SMYD2 has been associated with several diseases including Cancer. In the present study, we investigated whether and how SMYD2 might contribute to colorectal Cancer. Increased expression levels of SMYD2 were detected in human and murine colon tumor tissues compared to tumor-free tissues. SMYD2 deficiency in colonic tumor cells strongly decreased tumor growth in two independent experimental Cancer models. On a molecular level, SMYD2 deficiency sensitized colonic tumor cells to TNF-induced Apoptosis and Necroptosis without affecting cell proliferation. Moreover, we found that SMYD2 targeted RIPK1 and inhibited the phosphorylation of RIPK1. Finally, in a translational approach, pharmacological inhibition of SMYD2 attenuated colonic tumor growth. Collectively, our data show that SMYD2 is crucial for colon tumor growth and inhibits TNF-induced Apoptosis and Necroptosis.

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