Effect of Lipopolysaccharides on Liver Tumor Metastasis of twist1a/krasV12 Double Transgenic Zebrafish

Lu，Jeng Wei1,2; Lin，Liang In2,3; Sun，Yuxi1,4; Liu，Dong4; Gong，Zhiyuan1

2022

10.3390/biomedicines10010095

Biomedicines   影响因子和分区

2227-9059

The poor prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is directly associated with the multi-step process of tumor metastasis. TWIST1, a basic helix-loop-helix (bHLH) transcription factor, is the most important epithelial-mesenchymal transition (EMT) gene involved in embryonic development, tumor progression, and metastasis. However, the role that TWIST1 gene plays in the process of liver tumor metastasis in vivo is still not well understood. Zebrafish can serve as a powerful model for cancer research. Thus, in this study, we crossed twist1a+ and kras+ transgenic zebrafish, which, respectively, express hepatocyte-specific mCherry and enhanced green fluorescent protein (EGFP); they also drive overexpression of their respective transcription factors. This was found to exacerbate the development of metastatic HCC. Fluorescence of mCherry and EGFP-labeled hepatocytes revealed that approximately 37.5% to 45.5% of the twist1a+/kras+ double transgenic zebrafish exhibited spontaneous tumor metastasis from the liver to the abdomen and tail areas, respectively. We also investigated the inflammatory effects of lipopolysaccharides (LPS) on the hepatocyte-specific co-expression of twist1a+ and kras+ in double transgenic zebrafish. Following LPS exposure, co-expression of twist1a+ and kras+ was found to increase tumor metastasis by 57.8%, likely due to crosstalk with the EMT pathway. Our results confirm that twist1a and kras are important mediators in the development of metastatic HCC. Taken together, our in-vivo model demonstrated that co-expression of twist1a+/kras+ in conjunction with exposure to LPS enhanced metastatic HCC offers a useful platform for the study of tumor initiation and metastasis in liver cancer.

KrasV12 Lipopolysaccharides Liver tumor metastasis Transgenic zebrafish Twist1a

SCI

英语

其他

WOS:000758886500001

2-s2.0-85122258498

Scopus

1.Department of Biological Sciences,National University of Singapore,Singapore,117543,Singapore
2.Department of Clinical Laboratory Sciences and Medical Biotechnology,National Taiwan University,Taipei,10048,Taiwan
3.Department of Laboratory Medicine,National Taiwan University Hospital,Taipei,10048,Taiwan
4.Brain Research Center,School of Life Sciences,Southern University of Science and Technology,Shenzhen,518055,China

Lu，Jeng Wei,Lin，Liang In,Sun，Yuxi,et al. Effect of Lipopolysaccharides on Liver Tumor Metastasis of twist1a/krasV12 Double Transgenic Zebrafish[J]. Biomedicines,2022,10(1).

Lu，Jeng Wei,Lin，Liang In,Sun，Yuxi,Liu，Dong,&Gong，Zhiyuan.(2022).Effect of Lipopolysaccharides on Liver Tumor Metastasis of twist1a/krasV12 Double Transgenic Zebrafish.Biomedicines,10(1).

Lu，Jeng Wei,et al."Effect of Lipopolysaccharides on Liver Tumor Metastasis of twist1a/krasV12 Double Transgenic Zebrafish".Biomedicines 10.1(2022).