Cancer stem-like cell properties are regulated by EGFR/AKT/[beta]-catenin signaling and preferentially inhibited by gefitinib in nasopharyngeal carcinoma

• Published in: The FEBS journal 2013-05, Vol.280 (9), p.2027
• Main Authors: Ma, Lei, Zhang, Gong, Miao, Xiao-Bo, Deng, Xu-Bin, Wu, Yue, Liu, Ying, Jin, Zhi-Ru, Li, Xi-Qing, Liu, Qiu-Zhen, Sun, Du-Xin, Testa, Joseph R, Yao, Kai-Tai, Xiao, Guang-Hui
• Format: Article
• Language: English
• Subjects: Cancer; Signaling; Stem cells; Tumors
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.12226

We report that the epidermal growth factor receptor (EGFR) pathway plays a critical role in regulating cancer stem-like cells (CSCs) in nasopharyngeal carcinoma (NPC), one of the most common malignant tumors in Southeast Asia. Effects of EGFR on maintaining CSCs are mainly mediated by AKT signaling, and [beta]-catenin is responsible for governing CSC properties in response to EGFR/AKT activation. Significantly, CSCs are enriched by cisplatin and decreased by gefitinib in NPC xenograft models. Upon reimplantation in secondary mice, tumor cells derived from cisplatin-treated mice grew rapidly, whereas regrowth of tumor cells from gefitinib-treated mice was severely diminished. We further demonstrate that expression of EGFR correlates with expression of [beta]-catenin and Nanog in primary tumor specimens from NPC patients. These findings provide mechanistic and preclinical evidence supporting the use of gefitinib alone or in combination with a chemotherapeutic agent in first-line therapy for patients with NPC. In addition, our results suggest that targeting [beta]-catenin represents a rational clinical modality for patients whose tumors harbor activated EGFR or AKT. [PUBLICATION ABSTRACT]