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.

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.
Authors	Tasuku Mariya, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuta Tabuchi, Takuya Asano, Hiroshi Saijo, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tsuyoshi Saito, Noriyuki Sato
Journal	Oncotarget (Oncotarget) Vol. 7 Issue 18 Pg. 26806-22 (May 03 2016) ISSN: 1949-2553 [Electronic] United States
PMID	27072580 (Publication Type: Journal Article)
Chemical References	Biomarkers, Tumor MMP10 protein, human Matrix Metalloproteinase 10
Topics	Animals Biomarkers, Tumor (analysis) Carcinoma, Ovarian Epithelial Drug Resistance, Neoplasm (physiology) Enzyme Activation (physiology) Female Gene Expression Regulation, Neoplastic (physiology) Heterografts Humans Kaplan-Meier Estimate Matrix Metalloproteinase 10 (metabolism) Mice Mice, Nude Neoplasms, Glandular and Epithelial (metabolism, mortality, pathology) Neoplastic Stem Cells (metabolism, pathology) Ovarian Neoplasms (metabolism, mortality, pathology) Proportional Hazards Models Wnt Signaling Pathway (physiology)

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