Salt-inducible Kinase (SIK1) regulates HCC progression and WNT/β-catenin activation

Journal of Hepatology
Chao QuZhiyong Zhang

Abstract

In this study, we investigated the role of salt-inducible kinase 1 (SIK1) and its possible mechanisms in human hepatocellular carcinoma (HCC). Immunoprecipitation, immunohistochemistry, luciferase reporter, Chromatin immunoprecipitation, in vitro kinase assays and a mouse model were used to examine the role of SIK1 on the β-catenin signaling pathway. SIK1 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppresses epithelial-to-mesenchymal transition (EMT), tumor growth and lung metastasis in xenograft tumor models. The effect of SIK1 on tumor development occurs at least partially through regulation of β-catenin, as evidenced by the fact that SIK1 overexpression leads to repression of β-catenin transcriptional activity, while SIK1 depletion has the opposite effect. Mechanistically, SIK1 phosphorylates the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) at threonine (T)1391, which promotes the association of nuclear receptor corepressor (NCoR)/SMRT with transducin-beta-like protein 1 (TBL1)/transducing-beta-like 1 X-linked receptor 1 (TBLR1) and disrupts the binding of β-catenin to the TBL1/TBLR1 complex, thereby inactivating the Wnt/β-catenin pa...Continue Reading

References

May 1, 2007·Nature Medicine·Rebecca BerdeauxMarc Montminy
Jul 23, 2009·Science Signaling·Hailing ChengJean J Zhao
Sep 3, 2009·Science Signaling·Reuben J Shaw
Aug 4, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Melanie B ThomasAlan Venook
Oct 23, 2010·Molecular and Cellular Endocrinology·Natalia VarlakhanovaMartin L Privalsky
Jul 23, 2011·Molecular Cell·Hyo-Kyoung ChoiHo-Geun Yoon
Apr 3, 2012·The Biochemical Journal·Emma HenrikssonOlga Göransson
Aug 14, 2012·The Journal of Biological Chemistry·Eun-Jung AnnHee-Sae Park
Oct 22, 2013·Genes & Development·Jeff H Tsai, Jing Yang
Dec 31, 2014·Molecular Cancer Research : MCR·Hélène BonIan G Mills

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Citations

Nov 20, 2018·Nature Reviews. Gastroenterology & Hepatology·Maria J PerugorriaJesus M Banales
Jan 25, 2018·Journal of Hematology & Oncology·Man-Qing CaoZhao-You Tang
Oct 28, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Peng LiuXiao Xu
May 27, 2020·The Journal of Experimental Medicine·Qingxin ZhouZhiyong Zhang
Feb 22, 2018·Oncotarget·Michael VanlandewijckAristidis Moustakas
May 9, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fei MaZhiyong Zhang
Mar 10, 2020·World Journal of Gastroenterology : WJG·Long PanXiu-Jun Cai
Aug 28, 2020·World Journal of Gastroenterology : WJG·Zhao-Shan NiuLi-Mei-Li Tian
Mar 8, 2017·Expert Opinion on Drug Delivery·Lucia ScarabelBarbara Dapas
Mar 31, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rossella FarraBarbara Dapas
Jul 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Ling DengDehua Wu
Jun 3, 2020·Cell Death & Disease·Saihua HuangYufeng Zhou
Aug 14, 2020·Signal Transduction and Targeted Therapy·Zicheng SunJianping Guo
Jun 15, 2017·World Journal of Gastroenterology : WJG·Lin-Ling JuJian-Guo Shao
Dec 14, 2018·Experimental and Therapeutic Medicine·Xinping BaiYi Xu
Feb 17, 2021·Journal of Translational Medicine·Jinxiu HuZhimei Lv
Feb 9, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Dawei XuPengju Ma
Aug 14, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Xiaoyu FuYan Huang

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