title: Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2.
abstract: Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are important cellular components in the cancer microenvironment and may affect cancer phenotype and patient outcome. The nature of MDSCs and their interaction with CSCs in ovarian carcinoma are unclear. We examined the interaction between MDSCs and CSCs in patients with ovarian carcinoma and showed that MDSCs inhibited T cell activation and enhanced CSC gene expression, sphere formation, and cancer metastasis. MDSCs triggered miRNA101 expression in cancer cells. miRNA101 subsequently repressesed the corepressor gene C-terminal binding protein-2 (CtBP2), and CtBP2 directly targeted stem cell core genes resulting in increased cancer cell stemness and increasing metastatic and tumorigenic potential. Increased MDSC density and tumor microRNA101 expression predict poor survival, as does decreased tumor CtBP2 expression, independent of each other. Collectively, our work identifies an immune-associated cellular, molecular, and clinical network involving MDSCs-microRNA101-CtBP2-stem cell core genes, which extrinsically controls cancer stemness and impacts patient outcome.
authors.affiliation: Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Tracy X
authors.initials: TX
authors.lastname: Cui
authors.forename: Ilona
authors.initials: I
authors.lastname: Kryczek
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.forename: Ende
authors.initials: E
authors.lastname: Zhao
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.forename: Michael H
authors.initials: MH
authors.lastname: Roh
authors.forename: Linda
authors.initials: L
authors.lastname: Vatan
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szeliga
authors.forename: Yujun
authors.initials: Y
authors.lastname: Mao
authors.forename: Dafydd G
authors.initials: DG
authors.lastname: Thomas
authors.forename: Jan
authors.initials: J
authors.lastname: Kotarski
authors.forename: Rafał
authors.initials: R
authors.lastname: Tarkowski
authors.forename: Max
authors.initials: M
authors.lastname: Wicha
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cho
authors.forename: Thomas
authors.initials: T
authors.lastname: Giordano
authors.forename: Rebecca
authors.initials: R
authors.lastname: Liu
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D056970:Co-Repressor Proteins; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D056970:Co-Repressor Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human