PMID- 21281808
OWN - NLM
STAT- MEDLINE
DCOM- 20110523
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 178
IP  - 2
DP  - 2011 Feb
TI  - Tenascin C induces epithelial-mesenchymal transition-like change accompanied by 
      SRC activation and focal adhesion kinase phosphorylation in human breast cancer 
      cells.
PG  - 754-63
LID - 10.1016/j.ajpath.2010.10.015 [doi]
AB  - Tenascin C (TNC) is an extracellular matrix glycoprotein up-regulated in solid 
      tumors. Higher TNC expression is shown in invading fronts of breast cancer, which 
      correlates with poorer patient outcome. We examined whether TNC induces 
      epithelial-mesenchymal transition (EMT) in breast cancer. Immunohistochemical 
      analysis of invasive ductal carcinomas showed that TNC deposition was frequent in 
      stroma with scattered cancer cells in peripheral margins of tumors. The addition 
      of TNC to the medium of the MCF-7 breast cancer cells caused EMT-like change and 
      delocalization of E-cadherin and beta-catenin from cell-cell contact. Although 
      amounts of E-cadherin and beta-catenin were not changed after EMT in total lysates, 
      they were increased in the Triton X-100-soluble fractions, indicating movement 
      from the membrane into the cytosol. In wound healing assay, cells were scattered 
      from wound edges and showed faster migration after TNC treatment. The EMT 
      phenotype was correlated with SRC activation through phosphorylation at Y418 and 
      phosphorylation of focal adhesion kinase (FAK) at Y861 and Y925 of SRC substrate 
      sites. These phosphorylated proteins colocalized with alphav integrin-positive 
      adhesion plaques. A neutralizing antibody against alphav or a SRC kinase inhibitor 
      blocked EMT. TNC could induce EMT-like change showing loss of intercellular 
      adhesion and enhanced migration in breast cancer cells, associated with FAK 
      phosphorylation by SRC; this may be responsible for the observed promotion of TNC 
      in breast cancer invasion.
CI  - Copyright (c) 2011 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Nagaharu, Keiki
AU  - Nagaharu K
AD  - Department of Pathology and Matrix Biology, Graduate School of Medicine, Mie 
      University, Mie, Japan.
FAU - Zhang, Xinhui
AU  - Zhang X
FAU - Yoshida, Toshimichi
AU  - Yoshida T
FAU - Katoh, Daisuke
AU  - Katoh D
FAU - Hanamura, Noriko
AU  - Hanamura N
FAU - Kozuka, Yuji
AU  - Kozuka Y
FAU - Ogawa, Tomoko
AU  - Ogawa T
FAU - Shiraishi, Taizo
AU  - Shiraishi T
FAU - Imanaka-Yoshida, Kyoko
AU  - Imanaka-Yoshida K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Cadherins)
RN  - 0 (Integrin alphaV)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Tenascin)
RN  - 0 (beta Catenin)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Antibodies, Neutralizing/pharmacology
MH  - Breast Neoplasms/*enzymology/*pathology
MH  - Cadherins/metabolism
MH  - Cell Line, Tumor
MH  - Cell Membrane/drug effects/metabolism
MH  - Cell Movement/drug effects
MH  - Cytoplasm/drug effects/metabolism
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Female
MH  - Focal Adhesion Kinase 1/*metabolism
MH  - Humans
MH  - Integrin alphaV/immunology
MH  - Neoplasm Invasiveness
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Transport/drug effects
MH  - Stromal Cells/drug effects/pathology
MH  - Subcellular Fractions/metabolism
MH  - Tenascin/*pharmacology
MH  - Wound Healing/drug effects
MH  - beta Catenin/metabolism
MH  - src-Family Kinases/*metabolism
PMC - PMC3069868
EDAT- 2011/02/02 06:00
MHDA- 2011/05/24 06:00
PMCR- 2012/02/01
CRDT- 2011/02/02 06:00
PHST- 2010/01/03 00:00 [received]
PHST- 2010/10/14 00:00 [revised]
PHST- 2010/10/19 00:00 [accepted]
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/05/24 06:00 [medline]
PHST- 2012/02/01 00:00 [pmc-release]
AID - S0002-9440(10)00108-2 [pii]
AID - AJPA107 [pii]
AID - 10.1016/j.ajpath.2010.10.015 [doi]
PST - ppublish
SO  - Am J Pathol. 2011 Feb;178(2):754-63. doi: 10.1016/j.ajpath.2010.10.015.