Hepatitis B Virus HBx Activates Notch Signaling via Delta-Like 4/Notch1 in Hepatocellular Carcinoma

PloS One
Pornrat KongkavitoonTanapat Palaga

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
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
Jan 14, 2011·Journal of Gastroenterology and Hepatology·Michael C Kew
Sep 29, 2011·The Journal of Experimental Medicine·Camille LobryIannis Aifantis
Nov 2, 2012·Cancer Metastasis Reviews·Mausumi BharadwajShowket Hussain
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

❮ Previous
Next ❯

Citations

Aug 19, 2017·Viruses·Shaoli Lin, Yan-Jin Zhang
Mar 29, 2019·Clinical Epigenetics·Zeina NehmeGeorges Herbein
May 23, 2020·OncoTargets and Therapy·Meng-Xi XiuBo-Hai Kuang
Oct 13, 2016·World Journal of Gastroenterology : WJG·Areerat KunanopparatNattiya Hirankarn
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

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
PCR
Transfection
Protein Assay
flow cytometry
Assay

Software Mentioned

FlowJo
GraphPad Prism
ARCHITECT iSystem
SPSS

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis