Regulation of ERK and AKT pathways by hepatitis B virus X protein via the Notch1 pathway in hepatocellular carcinoma

Liao, Bo; Zhou, Honghao; Liang, Huifang; Li, Changhai

doi:10.3892/ijo.2017.4126

Cited by 23 publications

(15 citation statements)

References 31 publications

(38 reference statements)

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“… 88 HBx relieves the inhibition of ERK by activating Notch signaling, which promotes the growth of HCC. 89 HBcAg induces the upregulation of B7-H1 through the activation of the Akt, ERK, and P38 signaling pathways, which inhibits the clearance of HBV DNA and promotes the apoptosis of dendritic cells, 90 thereby benefiting HBV to evade immune surveillance.…”

Section: Hbv Involved In Activation Of Tumor-promoting Signaling Pathwaysmentioning

confidence: 99%

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

Yu¹,

Han²,

Zhao³

et al. 2021

JHC

115

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Hepatocellular carcinoma (HCC) is a common malignancy, and the hepatitis B virus (HBV) is its major pathogenic factor. Over the past decades, it has been confirmed that HBV infection could promote disease progression through a variety of mechanisms, ultimately leading to the malignant transformation of liver cells. Many factors have been identified in the pathogenesis of HBV-associated HCC (HBV-HCC), including HBV gene integration, genomic instability caused by mutation, and activation of cancer-promoting signaling pathways. As research in the progression of HBV-HCC progresses, the role of many new mechanisms, such as epigenetics, exosomes, autophagy, metabolic regulation, and immune suppression, is also being continuously explored. The occurrence of HBV-HCC is a complex process caused by interactions across multiple genes and multiple steps, where the synergistic effects of various cancer-promoting mechanisms accelerate the process of disease evolution from inflammation to tumorigenesis. In this review, we aim to provide a brief overview of the mechanisms involved in the occurrence and development of HBV-HCC, which may contribute to a better understanding of the role of HBV in the occurrence and development of HCC.

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Section: Hbv Involved In Activation Of Tumor-promoting Signaling Pathwaysmentioning

confidence: 99%

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

Yu¹,

Han²,

Zhao³

et al. 2021

JHC

115

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“…Interestingly, Zhou et al [ 20 ] reported that TRIP13 promotes the proliferation and invasion of epithelial ovarian cancer through Notch signaling pathway. Liao et al [ 21 ] found that hepatitis B virus X protein can activate the Notch pathway, thus promoting the development of liver cancer. In the study by Li et al [ 22 ] miR-1179 was found to inhibit the metastasis of breast cancer cells by inhibiting Notch signaling pathway and Hes1.…”

Section: Resultsmentioning

confidence: 99%

MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway

Xiong

et al. 2021

Cancer Cell Int

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Background Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized. Methods Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay. Results SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3′-untranslated region (3′UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells. Conclusion MiR-155-5p decreased the expression of SOX1 by binding to its 3′UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.

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“…All these in vitro as well as in vivo data have indicated an inhibition effect of EGFL8 on Notch signaling pathway in HCC. Furthermore, we treated EGFL8 depleted Hep3B cells with DAPT, an inhibitor of Notch signaling pathway [ 21 , 29 ], and found this treatment obviously inhibit the expression of Notch signaling pathway and significantly suppressed the migration, invasion, and survival of Hep3B cells which had been remarkably enhanced by EGFL8 knockdown, suggesting the modulation of EGFL8 on liver cancer cell metastasis and apoptosis is, at least partially, depend on the inhibition of Notch signaling pathway. However, the specific molecular mechanism underlying the regulation of EGFL8 on Notch signaling pathway remains to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway

Zhang

Guoqian

et al. 2021

BMC Cancer

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Background Our previous studies have reported the down-regulation of EGFL8 correlates to the development and prognosis of colorectal and gastric cancer. The present study is carried out to explore the expression pattern and role of EGFL8 in hepatocellular carcinoma (HCC). Methods and materials EGFL8 expression in 102 cases of HCC tissues matched with adjacent non-tumorous liver tissues, a normal liver cell line and three liver cancer cell lines with different metastatic capacity was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Moreover, the clinicopathological features and prognosis of HCC patients were correlated with expression of EGFL8. Subsequently, the gain-and loss-of-function experiments were carried out to investigate the biological function of EGFL8 in HCC. We also used N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-(S)- phenylglycine t-butyl ester (DAPT), an inhibitor for Notch signaling pathway, in these experiments to verify the involvement of Notch signaling pathway in the effects of EGFL8. Additionally, a mouse model was established to investigate the effect of EGFL8 on metastasis of HCC cells. The expression of Notch signaling pathway in HCC cells and xenograft mouse tumors were detected by Western blot and immunohistochemistory. Results The expression of EGFL8 was significantly decreased in HCC tissues and cell lines and EGFL8 down-regulation correlated to multiple nodules, vein invasion, high TNM stage and poor prognosis of HCC. Interestingly, the expression levels of EGFL8 in three liver cancer cell lines were negatively associated with their metastatic capacity. In vitro and in vivo experiments indicated that EGFL8 obviously suppressed metastasis and invasion of HCC cells but slightly promoted apoptosis. Meanwhile, the expression of Notch signaling pathway was obviously suppressed in EGFL8 overexpressed HCCLM3 cells and xenograft mouse tumors generated from these cells but markedly elevated in EGFL8 depleted Hep3B cells. Furthermore, the up-regulated expression of Notch signaling pathway and effects induced by EGFL8 knockdown in Hep3B cells could be counteracted by DAPT treatment. Conclusion The down-regulation of EGFL8 was correlated to progression and poor prognosis of HCC and regulates HCC cell migration, invasion and apoptosis through activating the Notch signaling pathway, suggesting EGFL8 as a novel therapeutic target and a potential prognostic marker for HCC.

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Regulation of ERK and AKT pathways by hepatitis B virus X protein via the Notch1 pathway in hepatocellular carcinoma

Cited by 23 publications

References 31 publications

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

The Mechanisms of HBV-Induced Hepatocellular Carcinoma

MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway

Down-regulation of EGFL8 regulates migration, invasion and apoptosis of hepatocellular carcinoma through activating Notch signaling pathway

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