Promoting epithelial-to-mesenchymal transition by D-kynurenine via activating aryl hydrocarbon receptor
| Autor: | Lu Li, Yan Li, Zhi-Qing Duan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Lung Neoplasms Clinical Biochemistry Vimentin Metastasis 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor medicine Humans Epithelial–mesenchymal transition Neoplasm Metastasis Molecular Biology Kynurenine biology Cadherin Mesenchymal stem cell Cell Biology General Medicine medicine.disease Aryl hydrocarbon receptor Cadherins Neoplasm Proteins 030104 developmental biology chemistry Receptors Aryl Hydrocarbon Cancer cell biology.protein Cancer research |
| Zdroj: | Molecular and cellular biochemistry. 448(1-2) |
| ISSN: | 1573-4919 |
| Popis: | Epithelial-to-mesenchymal transition (EMT) is believed to play key roles in the process of cancer metastasis. The molecular changes during EMT are characterized by the down-regulation of epithelial proteins, such as E-cadherin, and the up-regulation of mesenchymal proteins, such as vimentin (VIM). It has been demonstrated that L-kynurenine (L-Kyn), a physiological ligand of Aryl hydrocarbon receptor (Ahr), promotes cancer cells to metastasize. However, the effects of D-enantiomer of kynurenine, D-kynurenine (D-Kyn), on metastasis are still unclear. In the present paper, we firstly confirmed that D-Kyn (10, 40, 60, and 100 µM) positively regulated the metastasis of 95D cells, a lung cancer cell line, which was reduced upon siRNAAhr treatment. Moreover, significant enhancement VIM expression was detected in the presence of D-Kyn (10 and 40 µM). In contrast, 10 µM D-Kyn markedly attenuated E-cadherin level. Additionally, 10 µM D-Kyn-mediated changes of VIM and E-cadherin were substantially attenuated on siRNAAhr treatment as well. Most importantly, the evidences-10/40 µM D-Kyn-induced up-regulation of CYP1A1, 10 µM D-Kyn-induced increase of nuclear transfer of Ahr, and 10/40/60/100 µM D-Kyn-induced enhancement of DER-luciferase activity-indicated that D-Kyn was capable of activating Ahr in fact. These results suggest that D-Kyn increases lung cancer cells to metastasize by activating Ahr. |
| Databáze: | OpenAIRE |
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