title: Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer.
abstract: Previous studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial-mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer.
  
  
  
  First, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays.
  
  
  
  Expression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity.
  
  
  
  Taken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan. nagasakak-tky@umin.ac.jp.
authors.forename: Kazunori
authors.identifier: 0000-0002-0696-5175
authors.initials: K
authors.lastname: Nagasaka
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan. kkawana-tky@umin.org.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Taguchi
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Uehara
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Asaha
authors.initials: A
authors.lastname: Fujimoto
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Adachi
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagamatsu
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Arimoto
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D008565:Membrane Proteins; C509689:PARD3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: IL-6; Ovarian cancer; Par3; STAT3