Targeting Aryl Hydrocarbon Receptor with small molecule, 1′H-indole-3′-carbonyl -thiazole-4-carboxylic acid methyl ester blocked human glioma cell invasion via MYH9 [article]

li jiao Zhao, Qiu ting Shu, Hui Sun, Yun long Ma, Dan dan Kang, Ya ting Zhao, Jing Lu, Pei Gong, Fan Yang, fang Wan
2020 bioRxiv   pre-print
Aryl hydrocarbon receptor (AHR) was a master regulator of anti-tumor cell migration in various cell types. Whether and how AHR regulates glioma cell migration is largely unknown. We found that small molecule 2-(1H-indole-3-carbonyl) -thiazole -4- carboxylic acid methyl ester (ITE), an endogenous AHR ligand, can significantly block glioma cell migration and invasion in vitro, ex vivo and in vivo. Knocking down AHR by siRNA abolished ITE migration-inhibiting effects. ITE increased the number of
more » ... sed the number of filopodia-like protrusion formation, but reduced protrusion attachment to the extracellular matrix, and inhibited the rear retraction of migrating glioma cells. Moreover, both mesenchymal and amoeboid migrating cells were observed in the DMSO control group while none of the cells display amoeboid migration in the ITE treated group. MYH9 was significantly reduced by ITE treatment in human glioma cells. Over-expression of MYH9 abrogated ITE's migration-inhibiting effects, with the expression level of MYH9 correlated with cell migration ability. Since MYH9 is a component of non-muscle myosin IIA (NMIIA), which is essential for cell migration in 3D confined space, and not a discovered target of AHR, the fact that ITE affects MYH9 via AHR opens a new research and development avenue.
doi:10.1101/2020.01.13.903674 fatcat:kgyfewldwnah5ilotq7tsfbdwi