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Cancer stem‐like cell properties are regulated by EGFR / AKT /β–catenin signaling and preferentially inhibited by gefitinib in nasopharyngeal carcinoma
Author(s) -
Ma Lei,
Zhang Gong,
Miao XiaoBo,
Deng XuBin,
Wu Yue,
Liu Ying,
Jin ZhiRu,
Li XiQing,
Liu QiuZhen,
Sun DuXin,
Testa Joseph R.,
Yao KaiTai,
Xiao GuangHui
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12226
Subject(s) - gefitinib , nasopharyngeal carcinoma , cancer research , protein kinase b , epidermal growth factor receptor , egfr inhibitors , homeobox protein nanog , cancer stem cell , medicine , cisplatin , catenin , cancer , signal transduction , biology , wnt signaling pathway , radiation therapy , chemotherapy , microbiology and biotechnology , embryonic stem cell , induced pluripotent stem cell , gene , biochemistry
We report that the epidermal growth factor receptor ( EGFR ) pathway plays a critical role in regulating cancer stem‐like cells ( CSC s) in nasopharyngeal carcinoma ( NPC ), one of the most common malignant tumors in S outheast A sia. Effects of EGFR on maintaining CSC s are mainly mediated by AKT signaling, and β–catenin is responsible for governing CSC properties in response to EGFR / AKT activation. Significantly, CSC s 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 β–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 β–catenin represents a rational clinical modality for patients whose tumors harbor activated EGFR or AKT .