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Author Chen, Yi ♦ Xie, Xiaoyan ♦ Li, Xinyi ♦ Wang, Peiqi ♦ Jing, Qian ♦ Yue, Jiaqi ♦ Liu, Yang ♦ Cheng, Zhong ♦ Li, Jingyi ♦ Song, Haixing ♦ Li, Guoyu ♦ Liu, Rui ♦ Wang, Jinhui
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ AMPLIFICATION ♦ APPROXIMATIONS ♦ CELL PROLIFERATION ♦ CLINICAL TRIALS ♦ DIAGNOSIS ♦ DRUGS ♦ MAMMARY GLANDS ♦ MORTALITY ♦ NEOPLASMS ♦ WOMEN
Abstract Breast cancer, representing approximately 30% of all gynecological cancer cases diagnosed yearly, is a leading cause of cancer-related mortality for women. Amplification of FGFR1 is frequently observed in breast cancers and is associated with poor prognosis. Though FGFRs have long been considered as anti-cancer drug targets, and a cluster of FGFR antagonists are currently under clinical trials, the precise cellular responses under the treatment of FGFR antagonists remains unclear. Here, we show that PD166866, an FGFR1-selective inhibitor, inhibits proliferation and triggers anoikis in FGFR1-amplified breast cancer cell lines. Notably, we demonstrate that PD166866 induces autophagy in FGFR1-amplified breast cancer cell lines, while blockage of autophagy by Atg5 knockdown further enhances the anti-proliferative activities of PD166866. Moreover, mechanistic study reveals that PD166866 induces autophagy through repressing Akt/mTOR signaling pathway. Together, the present study provides new insights into the molecular mechanisms underlying the anti-tumor activities of FGFR antagonists, and may further assist the FGFRs-based drug discovery. -- Highlights: •FGFR1 antagonist inhibits cell viability in FGFR1-amplified breast cancer cells. •FGFR1 antagonist induces autophagy in FGFR1-amplified breast cancer cells. •FGFR1 antagonist-induced autophagy is protective. •FGFR1 antagonist induces autophagy by inhibiting Akt/mTOR pathway.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-05-20
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 474
Issue Number 1


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