Abstract
Hepatitis virus B (HBV) infection is one of the major causes of hepatocellular carcinomas (HCC). HBx protein encoded in HBV genome is one of the key viral factors leading to malignant transformation of infected cells. HBx functions by interfering with cellular functions, causing aberration in cellular behaviour and transformation. Notch signalling is a well-conserved pathway involved in cellular differentiation, cell survival and cell death operating in various types of cells. Aberration in the Notch signalling pathways is linked to various tumors, including HCC. The role of HBx on the Notch signalling in HCC, however, is still controversial. In this study, we reported that HBV genome-containing HCC cell line HepG2 (HepG2.2.15) expressed higher Notch1 and Delta-like 4 (Dll4), compared to the control HepG2 without HBV genome. This upregulation coincided with increased appearance of the cleavage of Notch1, indicating constitutively activated Notch signalling. Silencing of HBx specifically reduced the level of Dll4 and cleaved Notch1. The increase in Dll4 level was confirmed in clinical specimens of HCC lesion, in comparison with non-tumor lesions. Using specific signalling pathway inhibitors, we found that MEK1/2, PI3K/AKT and NF...Continue Reading
References
Feb 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·M A SellsG Acs
Apr 5, 2001·The Journal of Biological Chemistry·M ForguesX W Wang
Jan 19, 2002·Differentiation; Research in Biological Diversity·C MailhosD Ish-Horowicz
Jun 27, 2006·Oncogene·D KremsdorfC Brechot
Aug 31, 2006·The Journal of Biological Chemistry·Sung Gyoo ParkGuhung Jung
Dec 16, 2006·Current Molecular Medicine·Lucio MieleBarbara Osborne
Mar 16, 2007·Biochemical and Biophysical Research Communications·Juan GaoDaiming Fan
Dec 21, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Minhong Yan, Greg D Plowman
Jul 20, 2010·Cancer Letters·Fan WangBin Cheng
Jan 14, 2011·Journal of Gastroenterology and Hepatology·Michael C Kew
Sep 29, 2011·The Journal of Experimental Medicine·Camille LobryIannis Aifantis
Dec 17, 2011·PloS One·Qiuju HanZhigang Tian
Jan 6, 2012·Oncology Reports·Fan WangBin Cheng
Aug 23, 2012·PloS One·Sebastian MalmströmMagnus Lindh
Sep 19, 2012·Biotechnology Letters·Fan WangBin Cheng
Nov 2, 2012·Cancer Metastasis Reviews·Mausumi BharadwajShowket Hussain
Mar 2, 2013·International Journal of Oncology·Jing LuoBin Cheng
Oct 12, 2013·Journal of Cancer Research and Clinical Oncology·Zhaoguo LiuYin Lu
Jun 17, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fabian Geisler, Mario Strazzabosco
Jul 16, 2014·International Journal of Oncology·Qian SunBin Cheng
Jul 24, 2014·Methods in Molecular Biology·Shinya YamamotoHugo J Bellen
Aug 20, 2014·Nature Reviews. Urology·Angela N FloresLaure Marignol
Dec 30, 2014·Biomaterials·Ya-Rong LiuChao Fang
Citations
Nov 2, 2016·Frontiers in Cellular and Infection Microbiology·Xin WeiYe Zhang
Jun 3, 2017·Cell Death and Differentiation·Shao-Jun ZhouFu-Yao Liu
Aug 19, 2017·Viruses·Shaoli Lin, Yan-Jin Zhang
Mar 9, 2018·Mucosal Immunology·Ahmad Al-AttarOctavio A Gonzalez
Oct 23, 2019·Virologica Sinica·Shanshan XuWanhong Liu
Mar 29, 2019·Clinical Epigenetics·Zeina NehmeGeorges Herbein
Feb 9, 2019·Scientific Reports·Zijing WangShuichi Kaneko
May 23, 2020·OncoTargets and Therapy·Meng-Xi XiuBo-Hai Kuang
Nov 9, 2016·Journal of Experimental & Clinical Cancer Research : CR·Fanyun KongRenxian Tang
Oct 13, 2016·World Journal of Gastroenterology : WJG·Areerat KunanopparatNattiya Hirankarn
Oct 20, 2017·International Journal of Oncology·Bo LiaoChanghai Li
Jul 11, 2019·Oncology Letters·Yanbo KouRenxian Tang
Nov 15, 2016·Oncology Reports·Sheng-Li YangQian-Jin He
Sep 20, 2018·World Journal of Gastroenterology : WJG·Areerat KunanopparatNattiya Hirankarn
Feb 10, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Ricardo Cardoso CastroFabiani Gai Frantz
Apr 4, 2021·Cells·Catia GiovanniniLaura Gramantieri
May 14, 2021·Seminars in Liver Disease·Kazuma SekibaKazuhiko Koike
Jun 15, 2021·Frontiers in Cardiovascular Medicine·Randa M Breikaa, Brenda Lilly
Aug 24, 2021·Frontiers in Cell and Developmental Biology·Pankaj TrivediMaria Pia Felli