Expression of F-actin-capping protein subunit beta, CAPZB, is associated with cell growth and motility in epithelioid sarcoma

BMC Cancer

Research Article

Tsuyoshi Saito¹  Takashi Yao¹  Shinji Kohsaka²  Kazuo Kaneko³  Yoshiyuki Suehara³  Kenta Mukaihara³  Daisuke Kubota³  Midori Toda-Ishii⁴  Keisuke Akaike⁴  Marc Ladanyi⁵  Eisuke Kobayashi⁶  Tsutomu Fujimura⁷ 

[1] Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Medical Genomics Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan;Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Orthopedic Surgery, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Human Pathology, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, 113-8421, Tokyo, Japan;Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, 10065, New York, NY, USA;Division of Musculoskeletal Oncology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan;Laboratory of Biochemical Analysis, Central Laboratory of Medical Sciences, School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, 113-8421, Tokyo, Japan;

关键词: Ingenuity Pathway Analysis;    Epithelioid Sarcoma;    EpiS Cell;    Ingenuity Pathway Analysis Software;    Ingenuity Pathway Analysis Analysis;   

DOI  :  10.1186/s12885-016-2235-z

 received in 2015-04-16, accepted in 2016-03-01,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA 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.MethodsCellular 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.ResultsAll 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.ConclusionsCAPZB 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.

【 授权许可】

CC BY   
© Mukaihara et al. 2016