Epigenomic Reprogramming toward Mesenchymal-Epithelial Transition in Ovarian-Cancer-Associated Mesenchymal Stem Cells Drives Metastasis.

Autor:	Fan H; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA., Atiya HI; Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA., Wang Y; Department of Gynecology and Obstetrics, Department of Oncology, and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Pisanic TR; Johns Hopkins Institute for NanoBiotechnology, Johns Hopkins University, Baltimore, MD, USA., Wang TH; Johns Hopkins Institute for NanoBiotechnology, Johns Hopkins University, Baltimore, MD, USA., Shih IM; Department of Gynecology and Obstetrics, Department of Oncology, and Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Foy KK; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA., Frisbie L; Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA., Buckanovich RJ; Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Chomiak AA; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA., Tiedemann RL; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA., Rothbart SB; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA., Chandler C; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Shen H; Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, USA. Electronic address: hui.shen@vai.org., Coffman LG; Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee Women's Research Institute, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: coffmanl@upmc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Dec 08; Vol. 33 (10), pp. 108473.
DOI:	10.1016/j.celrep.2020.108473
Abstrakt:	A role for cancer cell epithelial-to-mesenchymal transition (EMT) in cancer is well established. Here, we show that, in addition to cancer cell EMT, ovarian cancer cell metastasis relies on an epigenomic mesenchymal-to-epithelial transition (MET) in host mesenchymal stem cells (MSCs). These reprogrammed MSCs, termed carcinoma-associated MSCs (CA-MSCs), acquire pro-tumorigenic functions and directly bind cancer cells to serve as a metastatic driver/chaperone. Cancer cells induce this epigenomic MET characterized by enhancer-enriched DNA hypermethylation, altered chromatin accessibility, and differential histone modifications. This phenomenon appears clinically relevant, as CA-MSC MET is highly correlated with patient survival. Mechanistically, mirroring MET observed in development, MET in CA-MSCs is mediated by WT1 and EZH2. Importantly, EZH2 inhibitors, which are clinically available, significantly inhibited CA-MSC-mediated metastasis in mouse models of ovarian cancer. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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