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2016 ; 7
(24
): 36800-36813
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gab.com Text
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English Wikipedia
C-terminus of MUC16 activates Wnt signaling pathway through its interaction with
?-catenin to promote tumorigenesis and metastasis
#MMPMID27167110
Liu Q
; Cheng Z
; Luo L
; Yang Y
; Zhang Z
; Ma H
; Chen T
; Huang X
; Lin SY
; Jin M
; Li Q
; Li X
Oncotarget
2016[Jun]; 7
(24
): 36800-36813
PMID27167110
show ga
MUC16/CA125 has been identified as a prominent cancer biomarker, especially for
epithelial ovarian cancers, in clinical test for over three decades. Due to its
huge mass, limited knowledge of MUC16 was acquired previously. By utilizing a
well characterized self-made MUC16 monoclonal antibody, we identified the
endogenous interaction between a C-terminal fragment of MUC16 (MUC16C) and
?-catenin for the first time, and further elucidated that trans-activation domain
of ?-catenin is required for this interaction. Such interaction could activate
the Wnt/?-catenin signaling pathway by facilitating cytosol-nucleus
transportation of ?-catenin, consequently induce cell proliferation and the
migration, eventually lead to tumorigenesis and metastasis in nude mice.
Consistently, knockdown of MUC16 significantly weakened the capabilities of cells
for proliferation and migration. Based on our discovery, we suggest that MUC16
appears as an attractive target for the development of effective anticancer
drugs.
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