title: CK2α/CSNK2A1 Phosphorylates SIRT6 and Is Involved in the Progression of Breast Carcinoma and Predicts Shorter Survival of Diagnosed Patients.
abstract: Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and protein kinase CK2 α1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells. In addition, CSNK2A1 was bound to SIRT6 and phosphorylated SIRT6; evidence for this is provided from immunofluorescence staining, co-immunoprecipitation of CSNK2A1 and SIRT6, a glutathione S-transferase pull-down assay, an in vitro kinase assay, and transfection of mutant CSNK2A1. Knockdown of SIRT6 decreased the proliferation and invasiveness of cancer cells. Overexpression of SIRT6 increased proliferation, but mutation at the Ser338 phosphorylation site of SIRT6 inhibited the proliferation of MCF7 cells. Moreover, both knockdown of SIRT6 and a mutation at the phosphorylation site of SIRT6 decreased expression of matrix metallopeptidase 9, β-catenin, cyclin D1, and NF-κB. Especially, SIRT6 expression was associated with the nuclear localization of β-catenin. This study demonstrates that CSNK2A1 and SIRT6 are indicators of poor prognosis for breast carcinomas and that CSNK2A1-mediated phosphorylation of SIRT6 might be involved in the progression of breast carcinoma.
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Jun Sang
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea.
authors.forename: See-Hyoung
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Urangoo
authors.initials: U
authors.lastname: Jamiyandorj
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Forensic Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Sang Jae
authors.initials: SJ
authors.lastname: Noh
authors.affiliation: Department of Orthopedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Jung Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Preventive Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Kwon
authors.affiliation: Department of Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Sung Hoo
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.affiliation: Department of Forensic Medicine, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Sylvester
authors.affiliation: Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea. Electronic address: kyjang@chonbuk.ac.kr.
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D016328:NF-kappa B; D051176:beta Catenin; D019938:Cyclin D1; C570325:CSNK2A1 protein, human; D047390:Casein Kinase II; C516592:SIRT6 protein, human; D037761:Sirtuins