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Galectin-3 supports stemness in ovarian cancer stem cells by activation of the Notch1 intracellular domain

 Hyeok Gu Kang  ;  Da-Hyun kim  ;  Seok-Jun Kim  ;  Yunhee Cho  ;  , Junghyun Jung  ;  Wonhee Jang  ;  Kyung-Hee Chun 
 ONCOTARGET , Vol.7(42) : 68229-68241, 2016 
Journal Title
Issue Date
Animals ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Female ; Galectin 3/genetics ; Galectin 3/metabolism* ; Gene Expression Regulation, Neoplastic ; Humans ; Mice, Nude ; Neoplastic Stem Cells/metabolism* ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism* ; Ovarian Neoplasms/pathology ; RNA Interference ; Receptor, Notch1/genetics ; Receptor, Notch1/metabolism* ; Spheroids, Cellular/metabolism ; Transplantation, Heterologous
Notch1 ; cancer stem cells ; galectin-3 ; ovarian cancer
Ovarian cancer is the most lethal gynecologic disease because usually, it is lately sensed, easily acquires chemoresistance, and has a high recurrence rate. Recent studies suggest that ovarian cancer stem cells (CSCs) are involved in these malignancies. Here, we demonstrated that galectin-3 maintains ovarian CSCs by activating the Notch1 intracellular domain (NICD1). The number and size of ovarian CSCs decreased in the absence of galectin-3, and overexpression of galectin-3 increased them. Overexpression of galectin-3 increased the resistance for cisplatin and paclitaxel-induced cell death. Silencing of galectin-3 decreased the migration and invasion of ovarian cancer cells, and overexpression of galectin-3 reversed these effects. The Notch signaling pathway was strongly activated by galectin-3 overexpression in A2780 cells. Silencing of galectin-3 reduced the levels of cleaved NICD1 and expression of the Notch target genes, Hes1 and Hey1. Overexpression of galectin-3 induced NICD1 cleavage and increased expression of Hes1 and Hey1. Moreover, overexpression of galectin-3 increased the nuclear translocation of NICD1. Interestingly, the carbohydrate recognition domain of galectin-3 interacted with NICD1. Overexpression of galectin-3 increased tumor burden in A2780 ovarian cancer xenografted mice. Increased expression of galectin-3 was detected in advanced stages, compared to stage 1 or 2 in ovarian cancer patients, suggesting that galectin-3 supports stemness of these cells. Based on these results, we suggest that targeting galectin-3 may be a potent approach for improving ovarian cancer therapy.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seok Jun(김석준)
Chun, Kyung Hee(전경희) ORCID logo https://orcid.org/0000-0002-9867-7321
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