title: Histone demethylase RBP2 is critical for breast cancer progression and metastasis.
abstract: Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis.
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: William K C
authors.initials: WK
authors.lastname: Cheung
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Minghui
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sophia Y
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: Siew Wee
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Section of Comparative Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Don X
authors.initials: DX
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: qin.yan@yale.edu.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C518459:RBP2 protein, human; D054840:Retinol-Binding Proteins, Cellular; D056466:Histone Demethylases