title: Expression of F-actin-capping protein subunit beta, CAPZB, is associated with cell growth and motility in epithelioid sarcoma.
abstract: BACKGROUND
  A previous proteomics study demonstrated the overexpression of F-actin capping protein subunit beta (CAPZB) in tissue specimens of epithelioid sarcoma (EpiS). The aim of the present study was to elucidate the function of CAPZB in EpiS.
  
  
  METHODS
  Cellular functional assays were performed in two EpiS cell lines using CAPZB siRNAs. In addition, comparative protein expression analyses using Isobaric Tags for Relative and Absolute Quantitation (i-TRAQ) method were performed to identify the specific proteins whose expression was dysregulated by CAPZB, and analysed the data with the Ingenuity Pathways Analysis (IPA) system using the obtained protein profiles to clarify the functional pathway networks associated with the oncogenic function of CAPZB in EpiS. Additionally, we performed functional assays of the INI1 protein using INI1-overexpressing EpiS cells.
  
  
  RESULTS
  All 15 EpiS cases showed an immunohistochemical expression of CAPZB, and two EpiS cell lines exhibited a strong CAPZB expression. Silencing of CAPZB inhibited the growth, invasion and migration of the EpiS cells. Analysis of protein profiles using the IPA system suggested that SWI/SNF chromatin-remodeling complexes including INI1 may function as a possible upstream regulator of CAPZB. Furthermore, silencing of CAPZB resulted in a decreased expression of INI1 proteins in the INI1-positive EpiS cells, whereas the induction of INI1 in the INI1-deficient EpiS cells resulted in an increased CAPZB mRNA expression.
  
  
  CONCLUSIONS
  CAPZB is involved in tumor progression in cases of EpiS, irrespective of the INI1 expression, and may be a potential therapeutic target. The paradoxical relationship between the tumor suppressor INI1 and the oncoprotein CAPZB in the pathogenesis of EpiS remains to be clarified.
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Mukaihara
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan. ysuehara@juntendo.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suehara
authors.affiliation: Department of Medical Genomics Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kohsaka
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kubota
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.|Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Toda-Ishii
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.|Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Akaike
authors.affiliation: Laboratory of Biochemical Analysis, Central Laboratory of Medical Sciences, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Division of Musculoskeletal Oncology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.affiliation: Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D051347:CapZ Actin Capping Protein / Q000096:biosynthesis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D000071796:SMARCB1 Protein / Q000096:biosynthesis / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction
chemical_list: C000598253:CAPZB protein, human; D051347:CapZ Actin Capping Protein; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human