Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer.
Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer.
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DOI：
10.18632/oncotarget.8645
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Sato N
中科院分区：
文献类型：
--
作者：
Mariya T;Hirohashi Y;Torigoe T;Tabuchi Y;Asano T;Saijo H;Kuroda T;Yasuda K;Mizuuchi M;Saito T;Sato N
上皮性卵巢癌（EOC）是女性最致命的癌症之一。据报道，癌症干细胞(CSCs)/癌起始细胞（CICs）是原发性和复发性癌症的起源，并且对几种治疗具有耐药性。本研究发现基质金属蛋白酶-10 （matrix metalloproteinase-10, MMP10）在EOC的CSCs/CICs中表达。一项免疫组织化学研究显示，在多变量分析中，MMP10的高表达水平是预后不良和铂耐药的标志。MMP10基因过表达实验和sirna敲低MMP10基因实验表明，MMP10在EOC中CSCs/CICs的维持和对铂试剂的抗性中发挥作用。此外，MMP10通过抑制非典型Wnt信号配体Wnt5a激活典型Wnt信号。因此，MMP10是EOC中CSCs/CICs的新标记物，靶向MMP10是EOC中化疗耐药CSCs/CICs的新途径。
Epithelial ovarian cancer (EOC) is one of the most lethal cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) have been reported to be origin of primary and recurrent cancers and to be resistant to several treatments. In this study, we identified matrix metalloproteinase-10 (MMP10) is expressed in CSCs/CICs of EOC. An immunohistochemical study revealed that a high expression level of MMP10 is a marker for poor prognosis and platinum resistance in multivariate analysis. MMP10 gene overexpression experiments and MMP10 gene knockdown experiments using siRNAs revealed that MMP10 has a role in the maintenance of CSCs/CICs in EOC and resistance to platinum reagent. Furthermore, MMP10 activate canonical Wnt signaling by inhibiting noncanonical Wnt signaling ligand Wnt5a. Therefore, MMP10 is a novel marker for CSCs/CICs in EOC and that targeting MMP10 is a novel promising approach for chemotherapy-resistant CSCs/CICs in EOC.
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DOI：
10.1038/nrc2644
发表时间：
2009-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.5
作者：
Cole, Megan F.;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
DOI：
10.1046/j.1432-1327.1998.2530067.x
发表时间：
1998-04-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Nakamura, H;Fujii, Y;Okada, Y
通讯作者：
Okada, Y
影响因子：
2.7
作者：
Jeng, AY;Chou, M;Parker, DT
通讯作者：
Parker, DT
影响因子：
3.3
作者：
Krampert, M;Bloch, W;Werner, S
通讯作者：
Werner, S