Melatonin inhibits tumorigenicity of glioblastoma stem-like cells via the AKT–EZH2–STAT3 signaling axis
Corresponding Author
Xueran Chen
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Correspondence
Xueran Chen and Zhiyou Fang, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Emails: [email protected] (XC) and [email protected] (ZF)
Search for more papers by this authorAijun Hao
Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, Shandong, China
Search for more papers by this authorXian Li
Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, Shandong, China
Search for more papers by this authorZhaoxia Du
Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, Shandong, China
Search for more papers by this authorHao Li
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Search for more papers by this authorHongzhi Wang
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Search for more papers by this authorHaoran Yang
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Search for more papers by this authorCorresponding Author
Zhiyou Fang
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Correspondence
Xueran Chen and Zhiyou Fang, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Emails: [email protected] (XC) and [email protected] (ZF)
Search for more papers by this authorCorresponding Author
Xueran Chen
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Correspondence
Xueran Chen and Zhiyou Fang, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Emails: [email protected] (XC) and [email protected] (ZF)
Search for more papers by this authorAijun Hao
Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, Shandong, China
Search for more papers by this authorXian Li
Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, Shandong, China
Search for more papers by this authorZhaoxia Du
Department of Histology and Embryology, Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, Shandong, China
Search for more papers by this authorHao Li
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Search for more papers by this authorHongzhi Wang
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Search for more papers by this authorHaoran Yang
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Search for more papers by this authorCorresponding Author
Zhiyou Fang
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China
Correspondence
Xueran Chen and Zhiyou Fang, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Emails: [email protected] (XC) and [email protected] (ZF)
Search for more papers by this authorAbstract
Glioblastoma stem-like cells (GSCs) displaying self-renewing and tumor-propagating capacity play a particularly important role in maintaining tumor growth, therapeutic resistance, and tumor recurrence. Therefore, new therapeutic strategies focusing on impairing GSC maintenance are urgently needed. Here, we used GSCs isolated from surgical specimens from patients with glioblastoma multiforme (GBM) to study the roles and underlying mechanisms associated with melatonin in GSC biology. The results showed that melatonin directly targeted glioma tumor cells by altering GSC biology and inhibiting GSC proliferation. Additionally, melatonin altered profile of transcription factors to inhibit tumor initiation and propagation. Furthermore, EZH2 S21 phosphorylation and EZH2–STAT3 interaction in GSCs were impaired following melatonin treatment. These results suggested that melatonin attenuated multiple key signals involved in GSC self-renewal and survival, and further supported melatonin as a promising GBM therapeutic.
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