scholarly journals Association of Epidermal Growth Factor and Epidermal Growth Factor Receptor Polymorphisms with the Risk of Hepatitis B Virus-Related Hepatocellular Carcinoma in the Population of North China

2013 ◽  
Vol 17 (8) ◽  
pp. 595-600 ◽  
Author(s):  
Jia Wu ◽  
Wei Zhang ◽  
Aiqiang Xu ◽  
Li Zhang ◽  
Tao Yan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Hepatitis B Virus ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Hepatitis B ◽  
North China ◽  
Growth Factor Receptor ◽  
B Virus ◽  
Epidermal Growth

scholarly journals The machinery for endocytosis of epidermal growth factor receptor coordinates the transport of incoming hepatitis B virus to the endosomal network

2019 ◽  
Vol 295 (3) ◽  
pp. 800-807 ◽  
Author(s):  
Masashi Iwamoto ◽  
Wakana Saso ◽  
Kazane Nishioka ◽  
Hirofumi Ohashi ◽  
Ryuichi Sugiyama ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Hepatitis B Virus ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Hepatitis B ◽  
Viral Infection ◽  
Growth Factor Receptor ◽  
Downstream Signaling ◽  
B Virus ◽  
Epidermal Growth

Sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the surface of human hepatocytes and functions as an entry receptor of hepatitis B virus (HBV). Recently, we have reported that epidermal growth factor receptor (EGFR) is involved in NTCP-mediated viral internalization during the cell entry process. Here, we analyzed which function of EGFR is essential for mediating HBV internalization. In contrast to the reported crucial function of EGFR-downstream signaling for the entry of hepatitis C virus (HCV), blockade of EGFR-downstream signaling proteins, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and signal transducer and activator of transcription (STAT), had no or only minor effects on HBV infection. Instead, deficiency of EGFR endocytosis resulting from either a deleterious mutation in EGFR or genetic knockdown of endocytosis adaptor molecules abrogated internalization of HBV via NTCP and prevented viral infection. EGFR activation triggered a time-dependent relocalization of HBV preS1 to the early and late endosomes and to lysosomes in concert with EGFR transport. Suppression of EGFR ubiquitination by site-directed mutagenesis or by knocking down two EGFR-sorting molecules, signal-transducing adaptor molecule (STAM) and lysosomal protein transmembrane 4β (LAPTM4B), suggested that EGFR transport to the late endosome is critical for efficient HBV infection. Cumulatively, these results support the idea that the EGFR endocytosis/sorting machinery drives the translocation of NTCP-bound HBV from the cell surface to the endosomal network, which eventually enables productive viral infection.

Trans-Activation of Epidermal Growth Factor Receptor Gene by the Hepatitis B Virus X-Gene Product

Virology ◽  
1993 ◽  
Vol 196 (2) ◽  
pp. 878-882 ◽  
Author(s):  
Stefano Menzo ◽  
Massimo Clementi ◽  
Elena Alfani ◽  
Patrizia Bagnarelli ◽  
Silvia Iacovacci ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Hepatitis B Virus ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Hepatitis B ◽  
Gene Product ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
B Virus ◽  
Epidermal Growth

NTCP oligomerization occurs downstream of the NTCP-EGFR interaction during hepatitis B virus internalization

2021 ◽  
Author(s):  
Kento Fukano ◽  
Mizuki Oshima ◽  
Senko Tsukuda ◽  
Hideki Aizaki ◽  
Mio Ohki ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Bile Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Entry ◽  
Sodium Taurocholate ◽  
Growth Factor Receptor ◽  
Host Cells ◽  
B Virus ◽  
Epidermal Growth

Sodium taurocholate cotransporting polypeptide (NTCP) is a receptor that is essential for hepatitis B virus (HBV) entry into the host cell. A number of HBV entry inhibitors targeting NTCP have been reported to date; these inhibitors have facilitated a mechanistic analysis of the viral entry process. However, the mechanism of HBV internalization into host cells after interaction of virus with NTCP remains largely unknown. Recently, we reported that troglitazone, a thiazolidinedione derivative, specifically inhibits both HBV internalization and NTCP oligomerization, resulting in inhibition of HBV infection. Here, using troglitazone as a chemical probe to investigate entry process, the contribution of NTCP oligomerization to HBV internalization was evaluated. Using surface plasmon resonance and transporter kinetics, we found that troglitazone directly interacts with NTCP and non-competitively interferes with NTCP-mediated bile acid uptake, suggesting that troglitazone allosterically binds to NTCP, rather than to the bile acid-binding pocket. Additionally, alanine scanning mutagenesis showed that a mutation at phenylalanine 274 of NTCP (F274A) caused a loss of HBV susceptibility and disrupted both the oligomerization of NTCP and HBV internalization without affecting viral attachment to the cell surface. An inhibitor of the interaction between NTCP and epidermal growth factor receptor (EGFR), another host cofactor essential for HBV internalization, impeded NTCP oligomerization. Meanwhile, co-immunoprecipitation analysis revealed that neither troglitazone nor the F274A mutation in NTCP affect the NTCP-EGFR interaction. These findings suggest that NTCP oligomerization is initiated downstream of the NTCP-EGFR interaction, and then triggers HBV internalization. This study provides significant insight into the HBV entry mechanisms. Importance Hepatitis B virus (HBV) infection is mediated by a specific interaction with sodium taurocholate cotransporting polypeptide (NTCP), a viral entry receptor. Although the virus-receptor interactions are believed to trigger viral internalization into host cells, the exact molecular mechanisms of HBV internalization are not understood. In this study, we revealed the mode of action whereby troglitazone, a specific inhibitor of HBV internalization, impedes NTCP oligomerization, and identified NTCP phenylalanine 274 as a residue essential for this oligomerization. We further analyzed the association between NTCP oligomerization and HBV internalization, a process that is mediated by epidermal growth factor receptor (EGFR), another essential host cofactor for HBV internalization. Our study provides critical information on the mechanism of HBV entry, and suggests that oligomerization of the viral receptor serves as an attractive target for drug discovery.

Interrupted crosstalk between natural killer cells and anti-epidermal growth factor receptor: a possible role in hepatocellular carcinoma treatment failure

2021 ◽  
Vol 21 ◽  
Author(s):  
Hadeer Abosalema ◽  
Shahenda Mahgoub ◽  
Mohamed Emara ◽  
Nahla Kotb ◽  
Sameh Soror
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Major Health Problem ◽  
Advanced Stages ◽  
Epidermal Growth ◽  
First Time ◽  
Late Stages

: Hepatocellular carcinoma (HCC) is a major health problem worldwide. Most patients are diagnosed for the first time at late stages; this leads to a very poor prognosis. It is challenging to discover strategies for treatment at these advanced stages. Recently, monoclonal antibodies (mAbs) targeting specific cellular signaling pathways in HCC have been developed. Unfortunately, they still have a low survival rate, and some of them failed clinically to produce effective responses even if they showed very good results against HCC in preclinical studies. This review focuses on and discusses the possible causes for the failure of mAbs, precisely anti-Epidermal Growth Factor Receptor (EGFR) mAb and the crosstalk between this mAb and patients' NK cells.

scholarly journals Immunohistochemical Expression of Epidermal Growth Factor Receptor in Hepatocellular Carcinoma

PRILOZI ◽  
2018 ◽  
Vol 39 (2-3) ◽  
pp. 21-28
Author(s):  
Dafina Nikolova ◽  
Viktorija Chalovska ◽  
Magdalena Genadieva Ivanova ◽  
Emilija Nikolovska ◽  
Ance Volkanovska ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tumor Cells ◽  
Liver Tissue ◽  
Vascular Invasion ◽  
Tumor Tissue ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Abstract Introduction: Epidermal growth factor receptor (EGFR) signaling plays an important role in various cancers, including hepatocellular carcinoma (HCC). We aimed to evaluate immunoexpression of EGFR in HCC and surrounding non-tumor liver tissue and to correlate it to multiple clinicopathologic data. Material and Methods: We analyzed 60 patients with HCC for multiple clinicopathologic characteristics and survival. Presence of the immunosignal and the percentage of positive tumor cells at the whole tumor tissue sample and adjacent cirrhotic liver tissue were semi-quantitatively determined. Results: Nineteen patients (31.67%) were female and 41 (68.33%) were male ranging in age from 31 to 85 years, median 61.88±10.51. Mean survival time for female patients was 8.86±1.76 months, for male 13.03±1.50 months and overall survival was 11.6051±1.19 months. The most patients had: T2 status (41.67%), no enlarged lymph nodes (90%), vascular invasion (63.33%) and well differentiated (43.33%) tumors. EGFR immunoexpression was determined in range from 0% to 100% in both tumor and non-tumor tissue with mean value of 39.58% in tumor and 86.86% in cirrhotic tissue (p<0.00). Higher percent of tumor EGFR positive cells were found in cases with higher T status, higher levels of AFP and poorly differentiated carcinoma, but not significantly. Lower percent of tumor EGFR positive cells were found in patients with vascular invasion and enlarged lymph nodes, but also not significantly. EGFR expression in tumor tissue significantly influenced survival of the patients (p<0.05). Conclusion: The study showed that expression of EGFR in lower percentage of tumor cells was associated to favorable prognosis, making it a potential prognostic marker and therapeutic target.

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