Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness <i>via</i> YAP/TAZ signaling pathway in non-small cell lung cancer cells

Xiu, Zihan; Liu, Jiao; Wu, Xin; Li, Xiangyong; Li, Sanzhong; Wu, Xiaofeng; Lv, Xiaohua; Ye, Hua; Tang, Xudong

doi:10.7150/jca.50512

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J Cancer 2021; 12(4):1169-1178. doi:10.7150/jca.50512 This issue Cite

Research Paper

Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells

Zihan Xiu^1#, Jiao Liu^1#, Xin Wu^2,3, Xiangyong Li¹, Sanzhong Li¹, Xiaofeng Wu¹, Xiaohua Lv², Hua Ye^2,3, Xudong Tang^1,2,3,4✉

1. Collaborative innovation center for antitumor active substance research and development, Institute of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang 524023, P.R. China.
2. Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Medical Research Institute of Guangdong Zhanjiang, Department of Pharmacology, Guangdong Medical University, Zhanjiang 524023, P.R. China.
3. Southern Marine Science and Engineering Guangdong Laboratory (Zhanjiang), Zhanjiang 524023, P.R. China.
4. Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Medical University, Dongguan 523808, P.R. China.
#These authors contributed equally to this work.

Citation:

Xiu Z, Liu J, Wu X, Li X, Li S, Wu X, Lv X, Ye H, Tang X. Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells. J Cancer 2021; 12(4):1169-1178. doi:10.7150/jca.50512. https://www.jcancer.org/v12p1169.htm

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Abstract

Our previous studies have isolated cytochalasin H (CyH) from endophytic fungus derived from mangrove and found that CyH induced apoptosis and inhibited migration and angiogenesis in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the effect of CyH on epithelial-mesenchymal transition (EMT) and cancer stemness of A549 and NCI-H460 NSCLC cells and the underlying mechanisms, especially the role of YAP/ TAZ signaling pathway in the process. Our results showed that CyH significantly inhibited invasive ability and the sphere formation of NSCLC cells. The expression of E-cadherin, an EMT epithelial marker, was obviously up-regulated, while the expression of Vimentin and N-cadherin, the EMT mesenchymal markers, was dramatically down-regulated by CyH treatment in NSCLC cells. Moreover, the expression of EMT-associated transcription factors including Slug, Twist1, and Snail1 and stemness markers including Nanog, Sox-2, and Oct-4 was significantly down-regulated by CyH treatment in NSCLC cells. Additionally, CyH significantly down-regulated YAP and TAZ expression and up-regulated LAST1/2 and MST1/2 expression, and CyH inhibited the interaction between YAP and TEAD. Furthermore, YAP knockdown abolished the effect of CyH on the expression of EMT- and stemness-related markers in NSCLC cells. Taken together, these results suggest that CyH inhibits EMT and cancer stemness of NSCLC cells via the regulation of YAP/TAZ signaling pathway.

Keywords: cytochalasin H (CyH), epithelial-mesenchymal transition (EMT), cancer stemness, YAP/TAZ, non-small cell lung cancer (NSCLC), mangrove

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APA

Xiu, Z., Liu, J., Wu, X., Li, X., Li, S., Wu, X., Lv, X., Ye, H., Tang, X. (2021). Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells. Journal of Cancer, 12(4), 1169-1178. https://doi.org/10.7150/jca.50512.

ACS

Xiu, Z.; Liu, J.; Wu, X.; Li, X.; Li, S.; Wu, X.; Lv, X.; Ye, H.; Tang, X. Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells. J. Cancer 2021, 12 (4), 1169-1178. DOI: 10.7150/jca.50512.

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CSE

Xiu Z, Liu J, Wu X, Li X, Li S, Wu X, Lv X, Ye H, Tang X. 2021. Cytochalasin H isolated from mangrove-derived endophytic fungus inhibits epithelial-mesenchymal transition and cancer stemness via YAP/TAZ signaling pathway in non-small cell lung cancer cells. J Cancer. 12(4):1169-1178.

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