title: Inhibition of STAT5a by Naa10p contributes to decreased breast cancer metastasis.
abstract: N-α-Acetyltransferase 10 protein (Naa10p, also called arrest-defective 1), the catalytic subunit of N-acetyltransferase A, is a critical regulator of cell death and proliferation. Naa10p is also shown to regulate cancer metastasis by inhibiting cell motility; however, its role in cancer metastasis is not fully understood. In this study, we found that high expression of Naa10p is positively correlated with the survival of patients with breast cancer, whereas negatively correlated with lymph node metastasis. Naa10p inhibits breast cancer cell migration and invasion in vitro and decreases the xenograft growth and metastasis in nude mice. Microarray screening revealed that Naa10p downregulates inhibitors of differentiation 1 (ID1) expression. Naa10p binds to signal transducer and activator of transcription 5a (STAT5a) and decreases STAT5a-stimulated ID1 expression in an acetyltransferase-independent manner. Moreover, Naa10p antagonizes Janus kinase 2-STAT5a signaling by lowering p65-activated interleukin-1β expression. Our results demonstrate a novel mechanism through which Naa10p inhibits the metastasis of breast cancer cells by targeting STAT5a.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China, Key Laboratory of Xinjiang Endemic and Ethnic Disease, School of Medicine, Shihezi University, Shihezi, Xinjiang 832000, China and.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Li
authors.initials: L
authors.lastname: Min
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Lin
authors.initials: L
authors.lastname: Meng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Breast Cancer Center.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathology and.
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Beihai
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Department of Biochemistry and Molecular Biology.
authors.forename: Chuanke
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, scc@bjcancer.org qulike@bjcancer.org.
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100142, China, scc@bjcancer.org.
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008207:Lymphatic Metastasis / Q000473:pathology; D053858:Metabolic Networks and Pathways; D051379:Mice; D008807:Mice, Inbred BALB C; D063209:N-Terminal Acetyltransferase A / Q000235:genetics / Q000378:metabolism*; D063213:N-Terminal Acetyltransferase E / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D053583:Interleukin-1beta; D016328:NF-kappa B; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E; C507924:JAK2 protein, human; D053614:Janus Kinase 2