ECHS1 acts as a novel HBsAg-binding protein enhancing apoptosis through the mitochondrial pathway in HepG2 cells

Xiao, Chuanxing; Yang, Xiao-Ning; Huang, Qiu‐An; Zhang, Yuqin; Lin, Biyun; Liu, Jingjing; Liu, Yunpeng; Jazag, Amarsanaa; Guleng, Bayasi; Ren, Jianlin

doi:10.1016/j.canlet.2012.11.030

Cited by 37 publications

(32 citation statements)

References 35 publications

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“…In recent years, roles in cancer cell proliferation and apoptosis have been reported for it. ECHS1 directly interacts with hepatitis B surface antigen (HBsAg) [18,24]. Binding of HBsAg reduces ECHS1 levels and induces apoptosis of the hepatocellular carcinoma HepG2 cells [18,25].…”

Section: Discussionmentioning

confidence: 99%

“…ECHS1 directly interacts with hepatitis B surface antigen (HBsAg) [18,24]. Binding of HBsAg reduces ECHS1 levels and induces apoptosis of the hepatocellular carcinoma HepG2 cells [18,25]. Proteomic analysis showed that ECHS1 expression is lower in hepatocellular carcinoma patients with hepatitis C virus infections [26].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, ECHS1 has been implicated in many cancers, including breast, prostate, colon and liver cancer [14][15][16][17][18][19]. ECHS1 levels were found to be elevated in needle biopsy samples from prostate cancer patients [16] and in liver cancer cells [17,18]. Reducing ECHS1 expression in hepatocellular carcinoma cells with shRNA inhibits PKB activation and tumor growth in xenograft mice [19].…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Zhu

Gao

Yichen

et al. 2014

Cellular and Molecular Biology Letters

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Enoyl coenzyme A hydratase short chain 1 (ECHS1) is an important part of the mitochondrial fatty acid β-oxidation pathway. Altered ECHS1 expression has been implicated in cancer cell proliferation. This study assessed ECHS1 expression in human gastric cancer cell lines and investigated the effects of ECHS1 knockdown on gastric cancer cell proliferation and migration. The human gastric cancer cell lines SGC-7901, BGC-823 and MKN-28, and the immortalized human gastric epithelial mucosa GES-1 cell line were analyzed for ECHS1 protein levels using western blot. The effectiveness of ECHS1-RNA interference was also determined using western blot. Proliferation and migration of the siECHS1 cells were respectively measured with the CCK-8 and transwell assays. Phosphorylation of PKB and GSK3β was assessed using western blot. ECHS1 protein levels were significantly higher in poorly differentiated cells than in well-differentiated cells and immortalized gastric epithelial mucosa cells. Stable expression of ECHS1 shRNA was associated with an over 41% reduction in the ECHS1 protein levels of siECHS1 cells. Constitutive knockdown of the ECHS1 gene in siECHS1 cells was associated with significantly inhibited cell proliferation and migration. We also observed decreased levels of PKB and GSK3β phosphorylation in siECHS1 cells. ECHS1 expression is increased in human gastric cancer cells. Increased ECHS1 expression activates PKB and GSK3β by inducing the phosphorylation of the two kinases. ECHS1 may play important roles in gastric cancer cell proliferation and migration through PKB- and GSK3β-related signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Zhu

Gao

Yichen

et al. 2014

Cellular and Molecular Biology Letters

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“…The interacting role between host proteins and S protein is another important mechanism leading to HCC. These proteins include JTB, ECHS1 and ALDOA, which refer to cell proliferation, cell motility and cell apoptosis [63][64][65] . More mechanisms need further research.…”

Section: Hepatitis B Surface Proteinsmentioning

confidence: 99%

Hepatitis B Virus-Related Hepatocellular Carcinoma: Pathogenic Mechanisms and Novel Therapeutic Interventions

Liu

Guleng

et al. 2014

Gastrointest Tumors

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Background: Infection with the hepatitis B virus (HBV) is one of most important risk factors for hepatocellular carcinoma (HCC). Indeed, HBV is considered a group 1 human carcinogen and is a highly oncogenic agent. HBV cannot be effectively controlled or completely eliminated, so chronic HBV infection is a public health challenge worldwide. Summary: It is now believed that HBV-induced HCC involves a complex interaction between multiple viral and host factors. Many factors contribute to HBV-associated HCC, including products of HBV, viral integration and mutation, and host susceptibility. This review outlines the main pathogenic mechanisms with a focus on those that suggest novel targets for the prevention and treatment of HCC. Key Message: HBV infection is an important risk factor for HCC. Understanding the interaction between viral and host factors in HBV-induced HCC will reveal potential targets for future therapies. Practical Implications: The two main therapeutic strategies consist of antiviral agents and immunotherapy-based approaches. Dendritic cell-based immunotherapy is promising for restoring the T cell-mediated antiviral immune response. Another approach is the specific expansion of the host's pool of HBV-specific T cells. Stimulation of the Toll-like receptors (TLRs), particularly TLR9, provides another means of boosting the antiviral response. Combination therapy with cytokines (interferon gamma and tumor necrosis factor alpha) plus lamivudine is more effective than these agents used alone. Therapeutic vaccines are being developed as an alternative to long-term antiviral treatment or as an adjunct.

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“…Molecular targeted therapies have become novel high throughput technologies to treat hepatocellular carcinoma, such as sorafenib, a multikinase inhibitor with survival benefits for advanced hepatocellular carcinoma patients [3]. Our previous study showed ECHS1 could bind to HBs and that ECHS1's localization in mitochondria induced HepG2 cell apoptosis [4]. So, we suggested that ECHS1 may be applied as a potential therapeutic target during HCC treatment.…”

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confidence: 99%

Silencing ECHS1 attenuates the proliferation and induces the autophagy of hepatocellular carcinoma via impairing cell metabolism and activating AMPK

Xu¹,

Chen²,

Chen³

et al. 2015

neo

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Hepatocellular carcinoma (HCC) is among the most common cancers in the world with a low survival rate. Our previous study showed Short chain enoyl-CoA hydratase (ECHS1) could bind to HBsAg (HBs) and that ECHS1's localization in mitochondria induced HepG2 cell apoptosis. However, the role of the ECHS1 in energy metabolism and autophagy during hepatocellular carcinoma development remains undefined. We aimed to determine what ECHS1 does to energy metabolism and its effects on HCC progression. We performed CCK-8, EdU assays in hepatocellular carcinoma cell lines (HepG2 and HuH7) with stable ECHS1 knock-down. ATP and NADP+/NADPH levels were measured using an colorimetric assay. Our data demonstrated that ECHS1 silencing inhibited cell proliferation and induced autophagy. ECHS1 knockdown did not increase fatty acid synthesis, but decreased cellular ATP. This resulted in AMP-activated protein kinase (AMPK) activation and induced HCC cell autophagy. Our results showed that silencing ECHS1 to attenuate proliferation and induce autophagy may make it a novel cancer therapy target.

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ECHS1 acts as a novel HBsAg-binding protein enhancing apoptosis through the mitochondrial pathway in HepG2 cells

Cited by 37 publications

References 35 publications

Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Attenuation of enoyl coenzyme A hydratase short chain 1 expression in gastric cancer cells inhibits cell proliferation and migration in vitro

Hepatitis B Virus-Related Hepatocellular Carcinoma: Pathogenic Mechanisms and Novel Therapeutic Interventions

Silencing ECHS1 attenuates the proliferation and induces the autophagy of hepatocellular carcinoma via impairing cell metabolism and activating AMPK

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