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The 14-3-3?/GSK3?/?-catenin/ZEB1 regulatory loop modulates chemo-sensitivity in
human tongue cancer
#MMPMID26036631
Peng C
; Jia X
; Xiong Y
; Yin J
; Li N
; Deng Y
; Luo K
; Zhang Q
; Wang C
; Zhang Z
; Zheng G
; He Z
Oncotarget
2015[Aug]; 6
(24
): 20177-89
PMID26036631
show ga
Here we demonstrated that chemotherapy induced 14-3-3? expression in tongue
cancer (TC) cells and overexpressed 14-3-3? sensitized TC cells to chemotherapy
especially in multidrug resistant TC (MDR-TC) cells. In agreement, 14-3-3?
knockdown enhanced resistance of TC cells to chemotherapy. Mechanically, we found
14-3-3? physically bound to GSK3? in protein level and the binding inhibited
?-catenin signaling. Coincidentally, chemotherapy as well as 14-3-3?
overexpression led to increase of GSK3? protein level. Increased GSK3? protein
sensitized TC cells to chemotherapy. Moreover, deregulation of
14-3-3?/GSK3?/?-catenin axis led to overexpressed ZEB1 in TC cells, especially in
MDR-TC cells. As a negative feedback loop, ZEB1 bond to 14-3-3? promoter to
enhance promoter hypermethylation in TC cells. Promoter hypermethylation resulted
into the decrease of 14-3-3? expression. Importantly, a positive correlation was
observed between 14-3-3? and GSK3? protein expression in TC tissues from patients
receiving chemotherapy. High levels of 14-3-3? and GSK3? were associated with
better prognosis in TC patients.
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