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PMID:17721995

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Citation

Zheng, Q, Safina, A and Bakin, AV (2008) Role of high-molecular weight tropomyosins in TGF-beta-mediated control of cell motility. Int. J. Cancer 122:78-90

Abstract

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.

Links

PubMed Online version:10.1002/ijc.23025

Keywords

Animals; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Breast Neoplasms/prevention & control; Cell Adhesion/physiology; Cell Movement/drug effects; Cell Movement/physiology; Collagen/metabolism; Drug Combinations; Humans; Immunoblotting; Laminin/metabolism; Lung Neoplasms/metabolism; Lung Neoplasms/prevention & control; Lung Neoplasms/secondary; Mammary Glands, Animal/metabolism; Mammary Glands, Animal/pathology; Matrix Metalloproteinases/metabolism; Mice; Mice, SCID; Molecular Weight; Neoplasm Invasiveness/pathology; Proteoglycans/metabolism; Rats; Transforming Growth Factor beta/pharmacology; Tropomyosin/genetics; Tropomyosin/metabolism; Tumor Cells, Cultured; Wound Healing

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TPM1

involved_in

GO:0045785: positive regulation of cell adhesion

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P04692

P

Seeded From UniProt

complete

HUMAN:TPM1

involved_in

GO:0042060: wound healing

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:P04692

P

Seeded From UniProt

complete

RAT:TPM1

involved_in

GO:0045785: positive regulation of cell adhesion

ECO:0000316: genetic interaction evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from

RAT:TPM1

involved_in

GO:0042060: wound healing

ECO:0000316: genetic interaction evidence used in manual assertion

P

Seeded From UniProt

Missing: with/from


See also

References

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