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

基质金属蛋白酶-10 通过激活经典 Wnt 信号来调节卵巢癌干细胞样细胞的干细胞性,并可成为化疗耐药性卵巢癌的靶点

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作者:Tasuku Mariya, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuta Tabuchi, Takuya Asano, Hiroshi Saijo, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tsuyoshi Saito, Noriyuki Sato

Abstract

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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