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Galectin-3 supports stemness in ovarian cancer stem cells by activation of the
Notch1 intracellular domain
#MMPMID27626163
Kang HG
; Kim DH
; Kim SJ
; Cho Y
; Jung J
; Jang W
; Chun KH
Oncotarget
2016[Oct]; 7
(42
): 68229-68241
PMID27626163
show ga
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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