ITE,an Endogenous Ligand Of AHR,inhibit GBM Cell Migration Via Down Regulation Of FAK/PYK2 Protein Level

Glioblastoma is a highly invasive central neural system tumor,can deeply invade into the parenchyma and can be not completely removed by surgery.The recurrence rate is high,and the recurrent tumors are more aggressive.Endogenous small molecule ITE is a ligand of ayrl hydrocarbon receptor,whose affinity for AhR is higher than another endogenous ligand kynurenin.In this project,we investigated the effects of ITE on glioma cell lines U87MG,U251 proliferation,migration and invasion,we found that ITE did not influent glioma cell lines'proliferation,but significantly inhibited cell migration and invasion,determined by scratch assay and Boyden chamber assay.siRNA kowndown of AhR abolished ITE's inhibition on cell migration and invastion,indicating ITE's effects require AhR.To explore the possible mechanisms,we determined ITE's effect on FAK/PYK2 pathway.We found that ITE can lower the protein levels of FAK and PYK2.ChIP-qPCR study revealed that ITE can promot the binding of AhR to the promoter of VAV3,but not that of FAK,suggesting that ITE may affect FAK's protein levels via non-transcription activity.Conclusion:ITE can inhibit the migration of U251 and U87MG cells,can lower the levels of FAK/PYK2 protein,and regulate the transcription of VAV3.