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Roles of Wnt/?-catenin signaling in the gastric cancer stem cells proliferation
and salinomycin treatment
#MMPMID24481453
Mao J
; Fan S
; Ma W
; Fan P
; Wang B
; Zhang J
; Wang H
; Tang B
; Zhang Q
; Yu X
; Wang L
; Song B
; Li L
Cell Death Dis
2014[Jan]; 5
(1
): e1039
PMID24481453
show ga
The Wnt1 protein, a secreted ligand that activates Wnt signaling pathways,
contributes to the self-renewal of cancer stem cells (CSCs) and thus may be a
major determinant of tumor progression and chemoresistance. In a series of
gastric cancer specimens, we found strong correlations among Wnt1 expression,
CD44 expression, and the grade of gastric cancer. Stable overexpression of Wnt1
increased AGS gastric cancer cells' proliferation rate and spheroids formation,
which expressed CSC surface markers Oct4 and CD44. Subcutaneous injection of nude
mice with Wnt1-overexpressing AGS cells resulted in larger tumors than injection
of control AGS cells. Salinomycin, an antitumor agent, significantly reduced the
volume of tumor caused by Wnt1-overexpressing AGS cells in vivo. This is achieved
by inhibiting the proliferation of CD44+Oct4+ CSC subpopulation, at least partly
through the suppression of Wnt1 and ?-catenin expression. Taken together,
activation of Wnt1 signaling accelerates the proliferation of gastric CSCs,
whereas salinomycin acts to inhibit gastric tumor growth by suppressing Wnt
signaling in CSCs. These results suggest that Wnt signaling might have a critical
role in the self-renewal of gastric CSCs, and salinomycin targeting Wnt signaling
may have important clinical applications in gastric cancer therapy.
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