DACT1 Overexpression in type I ovarian cancer inhibits malignant expansion and cis-platinum resistance by modulating canonical Wnt signalling and autophagy.
DACT1 Overexpression in type I ovarian cancer inhibits malignant expansion and cis-platinum resistance by modulating canonical Wnt signalling and autophagy.
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I 型卵巢癌中 DACT1 过表达通过调节经典 Wnt 信号传导和自噬抑制恶性扩张和顺铂耐药
DOI：
10.1038/s41598-017-08249-7
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发表时间：
2017-08-24
影响因子：
4.6
通讯作者：
Linghu H
中科院分区：
文献类型：
--
作者：
Li RN;Liu B;Li XM;Hou LS;Mu XL;Wang H;Linghu H
Type I epithelial ovarian cancer (EOC) is primarily resistant to platinum-based chemotherapies and needs novel therapeutics. Given the aberrant Wnt activation in type I EOC and the involvement of Dapper1 Antagonist of Catenin-1 (DACT1) in Wnt signalling, the role of DACT1 in tumourigenesis of type I EOC was evaluated. Firstly, all tested EOC cell lines and primary EOC tissues, especially type I EOC, were observed to have significantly lower DACT1 expression than normal controls. Next, 3AO cells, which arise from a patient with primary mucinous EOC and express low endogenous levels of DACT1, were transfected with a lentivirus carrying full-length DACT1 (3AO-DACT1), grew slower and formed smaller tumours in nude mice compared to 3AO-NC. Furthermore, 3AO-DACT1 had lower levels of key mediators of canonical Wnt signalling, Dvl2 and β-catenin, GSK-3β with phosphorylated Ser9, and the Wnt/β-catenin target genes, with significantly lower nuclear β-catenin levels. Additionally, 3AO-DACT which contained higher levels of lipidated LC3 (LC3-II) and Beclin1, but lower levels of p62/SQSTM1, were more sensitive to cis-platinum. And chloroquine partially rescued its cis-platinum resistance. We identified DACT1 as a negative regulator in type I EOC, protecting against malignant expansion by inhibiting canonical Wnt signalling and cis-platinum resistance by regulating autophagy.
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DOI：
10.1097/pas.0b013e3181cf3d79
发表时间：
2010-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kurman RJ;Shih IeM
通讯作者：
Shih IeM
影响因子：
11.8
作者：
Cheyette, BNR;Waxman, JS;Moon, RT
通讯作者：
Moon, RT
影响因子：
7.2
作者：
Gershenson, David M.;Sun, Charlotte C.;Bodurka, Diane C.
通讯作者：
Bodurka, Diane C.
影响因子：
4.8
作者：
Ma, Benyu;Liu, Bofeng;Chen, Ye-Guang
通讯作者：
Chen, Ye-Guang
影响因子：
5.3
作者：
Hsu, SC;Galceran, J;Grosschedl, R
通讯作者：
Grosschedl, R