PMID- 17721995
OWN - NLM
STAT- MEDLINE
DCOM- 20071220
LR  - 20200529
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 122
IP  - 1
DP  - 2008 Jan 1
TI  - Role of high-molecular weight tropomyosins in TGF-beta-mediated control of cell 
      motility.
PG  - 78-90
AB  - Transforming growth factor beta1 (TGF-beta1) suppresses tumor development at 
      early stages of cancer, but enhances tumor invasion and formation of metastasis. 
      TGF-beta1-mediated tumor invasion is associated with epithelial to mesenchymal 
      transition (EMT) and matrix proteolysis. The mechanisms of these TGF-beta1 
      responses in normal and tumor cells are not well understood. Recently, we have 
      reported that TGF-beta1 increases expression of high-molecular weight 
      tropomyosins (HMW-tropomyosins) and formation of actin stress fibers in normal 
      epithelial cells. The present study investigated the role of tropomyosin in 
      TGF-beta1-mediated cell motility and invasion. We found that TGF-beta1 restricts 
      motility of normal epithelial cells although it promotes EMT and formation of 
      actin stress fibers and focal adhesions. Cell motility was enhanced by 
      siRNA-mediated suppression of HMW-tropomyosins. TGF-beta1 stimulated migration 
      and matrix proteolysis in breast cancer MDA-MB-231 cells that express low levels 
      of HMW-tropomyosins. Tet-Off-regulated expression of HMW-tropomyosin inhibited 
      cell migration and matrix proteolysis without affecting expression of matrix 
      metalloproteinases. Tropomyosin increased cell adhesion to matrix by enhancing 
      actin fibers and focal adhesions. Finally, tropomyosin impaired the ability of 
      tumor cells to form lung metastases in SCID mice. Thus, these results suggest 
      that HMW-tropomyosins are important for TGF-beta-mediated control of cell 
      motility and acquisition of the metastatic potential.
CI  - Copyright 2007 Wiley-Liss, Inc.
FAU - Zheng, Qiao
AU  - Zheng Q
AD  - Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, 
      USA.
FAU - Safina, Alfiya
AU  - Safina A
FAU - Bakin, Andrei V
AU  - Bakin AV
LA  - eng
GR  - P30 CA016056/CA/NCI NIH HHS/United States
GR  - R01 CA095263/CA/NCI NIH HHS/United States
GR  - R01 CA95263/CA/NCI NIH HHS/United States
GR  - CA 16056/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (Tpm1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tropomyosin)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/metabolism/pathology/*prevention & control
MH  - Cell Adhesion/physiology
MH  - Cell Movement/*drug effects/physiology
MH  - Collagen/metabolism
MH  - Drug Combinations
MH  - Humans
MH  - Immunoblotting
MH  - Laminin/metabolism
MH  - Lung Neoplasms/metabolism/*prevention & control/secondary
MH  - Mammary Glands, Animal/metabolism/pathology
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Mice, SCID
MH  - Molecular Weight
MH  - Neoplasm Invasiveness/pathology
MH  - Proteoglycans/metabolism
MH  - Rats
MH  - Transforming Growth Factor beta/*pharmacology
MH  - Tropomyosin/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Wound Healing
EDAT- 2007/08/28 09:00
MHDA- 2007/12/21 09:00
CRDT- 2007/08/28 09:00
PHST- 2007/08/28 09:00 [pubmed]
PHST- 2007/12/21 09:00 [medline]
PHST- 2007/08/28 09:00 [entrez]
AID - 10.1002/ijc.23025 [doi]
PST - ppublish
SO  - Int J Cancer. 2008 Jan 1;122(1):78-90. doi: 10.1002/ijc.23025.