Abstract 4203: Alpha 9 nicotinic acetylcholine receptor promotes tumor progression in triple negative breast cancer
| Autor: | Jan-Show Chu, Hsiao-Feng Wang, Yuan Soon Ho, Yung Che Kuo, Victor J. Drew, Chi-Long Chen, Kha-Liang Lee, Yen Hua Huang, Wei-Zhan Zhuang |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Cancer Research. 78:4203-4203 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2018-4203 |
| Popis: | Purpose: To assess the potential therapeutic target on the alpha 9 nicotinic acetylcholine receptor (α9-nAChR) and the insulin-like growth factor (IGF)-I receptor (IGF-IR) for preventing distant metastasis in TNBC patients. Experimental Design: Expression levels of stemness-related genes, α9-nAChR and IGF-IR in clinical tissues (n = 67) were analyzed by RT-qPCR and the Pearson correlation analysis. The α9-nAChR, OCT4, IGF-1R, and p-IGF-1R protein in tissues were detected by immunohistochemical staining (n = 200). The effects of either α9-nAChR activation or IGF-1R transactivation on stemness expression in TNBC were examined using Western blot, ALDH activity assay with flow cytometry, shRNA silencing, wound closure/migration/invasion assay, as well as microCT scanning and IVIS assay for animal models. Results: A high positive correlation between the gene expression levels of OCT4/NANOG/CD24/CD44 and α9-nAChR/IGF-IR in human breast cancer tissues was observed. IGF-1R and OCT4 highly expressed in tumor part compared than that of in normal part. Moreover, IGF-1R positively correlated with OCT4 in tumor tissues. We also show that nicotine induced α9-nAChR activation trans-activates the expression of IGF-1R and pluripotent protein OCT4, which mediated stemness-related properties in TNBC cell lines. Our results reveal that knockdown α9nAChR and IGF-1R diminish the pernicious effects of nicotine, inhibit stemness activities, and suppress metastasis both in vitro and in vivo. Conclusions: A crosstalk between α9-nAChR and IGF-IR signal mediates the stemness-related properties and metastasis therefore convene poor prognosis in TNBCs. Citation Format: Yung-Che Kuo, Jan-Show Chu, Kha-Liang Lee, Hsiao-Feng Wang, Victor James Drew, Wei-Zhan Zhuang, Chi-Long Chen, Yuan-Soon Ho, Yen-Hua Huang. Alpha 9 nicotinic acetylcholine receptor promotes tumor progression in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4203. |
| Databáze: | OpenAIRE |
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