PMID- 32805233
OWN - NLM
STAT- MEDLINE
DCOM- 20201201
LR  - 20201201
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 190
IP  - 11
DP  - 2020 Nov
TI  - S100A4/Nonmuscle Myosin IIA/p53 Axis Contributes to Aggressive Features in 
      Ovarian High-Grade Serous Carcinoma.
PG  - 2304-2316
LID - S0002-9440(20)30373-4 [pii]
LID - 10.1016/j.ajpath.2020.07.014 [doi]
AB  - S100A4 is a small calcium-binding protein that exerts its biological functions by 
      interacting with nonmuscle myosin IIA (NMIIA) and p53. Although S100A4 promotes 
      metastasis in several tumors, little is known about its involvement in the 
      progression of ovarian high-grade serous carcinomas (HGSCs). Herein, we focused 
      on functional roles of the S100A4/NMIIA/p53 axis in these tumors. In HGSC cell 
      lines harboring mutant p53, knockdown (KD) of S100A4 reduced the expression of 
      several epithelial-mesenchymal transition/cancer stem cell markers and the 
      ALDH1(high) population, consistent with an inhibition of stemness features. 
      S100A4-KD also increased apoptosis, decreased cell proliferation, and accelerated 
      cell mobility. This was accompanied by increased Snail expression, which, in 
      turn, was likely due to loss of p53 function. In contrast, specific inhibition of 
      NMIIA by blebbistatin induced phenotypes that-with the exception of cell 
      proliferation and mobility-were opposite to those observed in S100A4-KD cells. In 
      clinical samples, cytoplasmic and/or nuclear interactions between S100A4, NMIIA, 
      and mutant p53 were observed. In addition, high expression of S100A4, but not 
      NMIIA or p53, was a significant and independent unfavorable prognostic factor in 
      HGSC patients. These findings suggest that, via its interaction with NMIIA and 
      p53, overexpressed S100A4 may induce epithelial-mesenchymal transition/cancer 
      stem cell properties in HGSC and elicit several other tumor-associated 
      phenotypes.
CI  - Copyright (c) 2020 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Hiruta, Ai
AU  - Hiruta A
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Oguri, Yasuko
AU  - Oguri Y
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Yokoi, Ako
AU  - Yokoi A
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Matsumoto, Toshihide
AU  - Matsumoto T
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Oda, Yusuke
AU  - Oda Y
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Tomohiro, Mikihisa
AU  - Tomohiro M
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Hashimura, Miki
AU  - Hashimura M
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Jiang, Zesong
AU  - Jiang Z
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Tochimoto, Masataka
AU  - Tochimoto M
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Nakagawa, Mayu
AU  - Nakagawa M
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan.
FAU - Saegusa, Makoto
AU  - Saegusa M
AD  - Department of Pathology, Kitasato University School of Medicine, Sagamihara, 
      Japan. Electronic address: msaegusa@med.kitasato-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200815
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (S100 Calcium-Binding Protein A4)
RN  - 0 (SNAI1 protein, human)
RN  - 0 (Snail Family Transcription Factors)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 142662-27-9 (S100A4 protein, human)
RN  - EC 3.6.1.- (Nonmuscle Myosin Type IIA)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cystadenocarcinoma, Serous/*metabolism/pathology
MH  - Epithelial-Mesenchymal Transition
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Neoplastic Stem Cells/*metabolism/pathology
MH  - Nonmuscle Myosin Type IIA/*metabolism
MH  - Ovarian Neoplasms/*metabolism/pathology
MH  - S100 Calcium-Binding Protein A4/*metabolism
MH  - *Signal Transduction
MH  - Snail Family Transcription Factors/biosynthesis
MH  - Tumor Suppressor Protein p53/*metabolism
EDAT- 2020/08/18 06:00
MHDA- 2020/12/02 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/05/09 00:00 [received]
PHST- 2020/07/02 00:00 [revised]
PHST- 2020/07/21 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2020/12/02 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - S0002-9440(20)30373-4 [pii]
AID - 10.1016/j.ajpath.2020.07.014 [doi]
PST - ppublish
SO  - Am J Pathol. 2020 Nov;190(11):2304-2316. doi: 10.1016/j.ajpath.2020.07.014. Epub 
      2020 Aug 15.