RETRACTED ARTICLE: Chemical inhibition reveals differential requirements of signaling pathways in krasV12- and Myc-induced liver tumors in transgenic zebrafish

Bai, Guangdong; Yang, Qiqi; Huo, Xiaojing; Li, Hankun; Zhou, Li; Gong, Zhiyuan

doi:10.1038/srep45796

Cited by 15 publications

(12 citation statements)

References 46 publications

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“…In fact, the co-induction of twist1a and xmrk resulted in a 31% increase in the number of apoptotic cells ( Figure 4 A,C). These findings are consistent with those of our previous research on HCC development in other oncogene transgenic zebrafish [ 31 , 35 ]. Remarkably, the percentage of apoptotic cells was higher in transgenic zebrafish with twist1a+ / xmrk+ than in the xmrk+ induction group ( Figure 4 C).…”

Section: Resultssupporting

confidence: 94%

Exacerbation of Liver Tumor Metastasis in twist1a+/xmrk+ Double Transgenic Zebrafish following Lipopolysaccharide or Dextran Sulphate Sodium Exposure

Sun

Lin

et al. 2021

Pharmaceuticals

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The poor prognosis for patients with hepatocellular carcinoma (HCC) is related directly to metastasis. The Twist1 gene encodes for a transcription factor essential to embryogenesis. It has also been shown to promote epithelial-to-mesenchymal transition (EMT), invasion, and metastasis; however, there is currently no in vivo evidence that Twist1 plays a role in the metastasis of liver tumors. Zebrafish are increasingly being used as an alternative cancer model. In the current study, an adult-stage zebrafish HCC model was used to examine the synergistic effects of twist1a and xmrk, a well characterized oncogene, during HCC metastasis. We also examined the effects of two inflammatory agents, lipopolysaccharides (LPS) and dextran sulfate sodium (DSS), on the hepatocyte-specific expression of transgenic twist1a and xmrk. The conditional overexpression of twist1a and xmrk was shown to promote liver tumor metastasis in zebrafish, resulting in increased apoptosis and cell proliferation as well as tumor maintenance and propagation independent of the inherent EMT-inducing activity of xmrk. Exposing twist1a+/xmrk+ transgenic zebrafish to LPS or DSS was shown to promote metastasis, indicating that the overexpression of twist1a and xmrk led to crosstalk between the signaling pathways involved in EMT. This study provides important evidence pertaining to the largely overlooked effects of signaling crosstalk between twist1a and xmrk in regulating HCC metastasis. Our results also suggest that the co-expression of twist1a/xmrk in conjunction with exposure to LPS or DSS enhances HCC metastasis, and provides a valuable in vivo platform by which to investigate tumor initiation and metastasis in the study of liver cancer.

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Section: Resultssupporting

confidence: 94%

Exacerbation of Liver Tumor Metastasis in twist1a+/xmrk+ Double Transgenic Zebrafish following Lipopolysaccharide or Dextran Sulphate Sodium Exposure

Sun

Lin

et al. 2021

Pharmaceuticals

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“…3D ). These histological characteristics reproduce the typical morphology and growth patterns of tumors seen in zebrafish 26 . Notice however that although the histo-pathological examination revealed typical tumor morphology, the expression of CFP (and the concomitant oncogene) was no longer detected (Fig.…”

Section: Resultssupporting

confidence: 72%

Optical Control of Tumor Induction in the Zebrafish

Feng

Nam

Hamouri

et al. 2017

Sci Rep

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The zebrafish has become an increasingly popular and valuable cancer model over the past few decades. While most zebrafish cancer models are generated by expressing mammalian oncogenes under tissue-specific promoters, here we describe a method that allows for the precise optical control of oncogene expression in live zebrafish. We utilize this technique to transiently or constitutively activate a typical human oncogene, kRASG12V, in zebrafish embryos and investigate the developmental and tumorigenic phenotypes. We demonstrate the spatiotemporal control of oncogene expression in live zebrafish, and characterize the different tumorigenic probabilities when kRASG12V is expressed transiently or constitutively at different developmental stages. Moreover, we show that light can be used to activate oncogene expression in selected tissues and single cells without tissue-specific promoters. Our work presents a novel approach to initiate and study cancer in zebrafish, and the high spatiotemporal resolution of this method makes it a valuable tool for studying cancer initiation from single cells.

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“…We have previously generated several inducible HCC models in zebrafish by overexpression of an oncogene specifically in hepatocytes [9] , [10] , [11] , [12] , [13] . In our kras V12 -expressing zebrafish HCC model, we have observed a significant liver enlargement in 6-dpf (day post fertilization) larvae after 3 days of induction of kras V12 expression [14] . In the current study, we found that after 4 days of doxycycline exposure, both HSC density and ratio of activation were increased significantly.…”

Section: Introductionmentioning

confidence: 72%

RETRACTED: Activation of Hepatic Stellate Cells During Liver Carcinogenesis Requires Fibrinogen/Integrin αvβ5 in Zebrafish

2018

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Hepatocellular carcinoma (HCC) is one of the most common cancers and it usually develops from a background of liver fibrosis or inflammation. The crosstalk between tumor cells and stromal cells plays an important and stimulating role during tumor progression. Previously we found in a krasV12–induced zebrafish HCC model that oncogenic hepatocytes activate hepatic stellate cells (HSCs) by up-regulation of serotonin and activate neutrophils and macrophages by up-regulation of cortisol. In the present study, we found a novel signaling transduction mechanism between oncogenic hepatocytes and HSCs. After krasV12 induction, fibrinogen was up-regulated in oncogenic hepatocytes. We reasoned that fibrinogen may bind to integrin αvβ5 on HSCs to activate HSCs. Consistent with this notion, pharmaceutical treatment using an antagonist of integrin αvβ5, cilengitide, significantly blocked HSC activation and function, accompanied by attenuated proliferation of oncogenic hepatocytes and progression of liver fibrosis. On the contrary, adenosine 5’-diphosphate, an agonist of αvβ5, activated HSCs significantly that further stimulated the tumor progression and liver fibrosis. Interestingly, in human liver disease samples, we detected an increased level of fibrinogen during tumor progression which indicated the potential role of fibrinogen signaling in HCC progression. Thus, we concluded a novel interaction between oncogenic hepatocytes and HSCs through the fibrinogen related pathway in both the zebrafish HCC model and human liver disease samples.

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RETRACTED ARTICLE: Chemical inhibition reveals differential requirements of signaling pathways in krasV12- and Myc-induced liver tumors in transgenic zebrafish

Cited by 15 publications

References 46 publications

Exacerbation of Liver Tumor Metastasis in twist1a+/xmrk+ Double Transgenic Zebrafish following Lipopolysaccharide or Dextran Sulphate Sodium Exposure

Exacerbation of Liver Tumor Metastasis in twist1a+/xmrk+ Double Transgenic Zebrafish following Lipopolysaccharide or Dextran Sulphate Sodium Exposure

Optical Control of Tumor Induction in the Zebrafish

RETRACTED: Activation of Hepatic Stellate Cells During Liver Carcinogenesis Requires Fibrinogen/Integrin αvβ5 in Zebrafish

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