Abstract 5739: Nicotine promotes stemness-related properties and cell migration/metastasis through IGF-1R regulation in triple negative breast cancer
| Autor: | Kha-Liang Lee, Yung Che Kuo, Wei-Zhan Zhuang, Yuan Soon Ho, Chi-Long Chen, Jan-Show Chu, Yen Hua Huang, Victor J. Drew |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Cancer Research. 77:5739-5739 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2017-5739 |
| Popis: | Purpose: To determine the role of insulin-like growth factor (IGF)-I receptor (IGF-IR) in alpha 9 nicotinic acetylcholine receptor (α9-nAChR)-induced stemness-related properties and to assess the therapeutic potential for preventing early tumor relapse and metastasis of TNBCs. Experimental Design: Expression levels of stemness-related genes, α9-nAChR and IGF-IR in tissues (n = 67) were analyzed by real-time Q-PCR and the correlation of different gene levels were calculated by the Pearson correlation analysis. The effects of either α9-nAChR activation or IGF-1R transactivation on stemness expression in TNBC were examined using ALDEFLUOR assay with flow cytometry, RNA interference, wound closure/migration/invasion assay, and animal models. The α9-nAChR, OCT4 and IGF-1R protein, p-IGF-1R in tissues were detected by immunohistochemical staining. 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. Nicotine induced α9-nAChR activation trans-activates an IGF-IR expression and a phosphorylation of STAT3, which stimulated stemness-related properties in both the cell lines and the xenografted mouse tumors. The inhibition of either α9-nAChR or IGF-IR activation by RNA interference significantly suppressed the nicotine-induced stemness-related properties and cell metastasis both in vitro and in vivo. Conclusions: IGF-1R signal regulates the nicotine/α9-nAChR-induced stemness properties and cell metastasis therefore convene poor prognosis in TNBCs. Citation Format: Yung-Che Kuo, Jan-Show Chu, Kha-Liang Lee, Victor James Drew, Wei-Zhan Zhuang, Chi-Long Chen, Yuan-Soon Ho, Yen-Hua Huang. Nicotine promotes stemness-related properties and cell migration/metastasis through IGF-1R regulation in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5739. doi:10.1158/1538-7445.AM2017-5739 |
| Databáze: | OpenAIRE |
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