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Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis

The E‐cadherin/catenin cell adhesion system is often down‐regulated in epithelial tumors. This is thought to play an important role in cancer invasion and metastasis, and restoration of this system may suppress metastatic spread of cancer. In this study, the effects of a Ras farnesylation inhibitor...

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Autores principales: Nam, Jeong‐Seok, Ino, Yoshinori, Sakamoto, Michiie, Hirohashi, Setsuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2002
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927130/
https://www.ncbi.nlm.nih.gov/pubmed/12359056
http://dx.doi.org/10.1111/j.1349-7006.2002.tb02479.x
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author Nam, Jeong‐Seok
Ino, Yoshinori
Sakamoto, Michiie
Hirohashi, Setsuo
author_facet Nam, Jeong‐Seok
Ino, Yoshinori
Sakamoto, Michiie
Hirohashi, Setsuo
author_sort Nam, Jeong‐Seok
collection PubMed
description The E‐cadherin/catenin cell adhesion system is often down‐regulated in epithelial tumors. This is thought to play an important role in cancer invasion and metastasis, and restoration of this system may suppress metastatic spread of cancer. In this study, the effects of a Ras farnesylation inhibitor (FTI‐277) on E‐cadherin‐mediated cell‐cell adhesion and metastatic potential were examined. In cell aggregation assays, FTI‐277 stimulated aggregation of colon, liver and breast cancer cells. In vitro cultures of cancer cells showed that FIT‐277 induced strong cell‐cell contact. Immunoblotting analysis showed that FTI‐277 increased E‐cadherin/catenin (α, β and γ) expression and strongly stabilized E‐cadherin/catenin with the actin cytoskeleton. Northern blotting studies indicated that the observed increase in the E‐cadherin/catenin protein content was due to increased expression of their genes. After inoculation of the spleens of mice with severe combined immunodeficiency (SCID) with cancer cells, FTI‐277 treatment for 3 weeks markedly reduced splenic primary tumor growth and the rate of liver metastasis compared with control counterparts. Our data demonstrate that FTI‐277 can activate functioning of the E‐cadherin‐mediated cell adhesion system, which is associated with suppression of cancer cell metastasis. Therefore, selective inhibition of Ras activation may be useful for preventing cancer metastasis.
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spelling pubmed-59271302018-05-11 Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis Nam, Jeong‐Seok Ino, Yoshinori Sakamoto, Michiie Hirohashi, Setsuo Jpn J Cancer Res Article The E‐cadherin/catenin cell adhesion system is often down‐regulated in epithelial tumors. This is thought to play an important role in cancer invasion and metastasis, and restoration of this system may suppress metastatic spread of cancer. In this study, the effects of a Ras farnesylation inhibitor (FTI‐277) on E‐cadherin‐mediated cell‐cell adhesion and metastatic potential were examined. In cell aggregation assays, FTI‐277 stimulated aggregation of colon, liver and breast cancer cells. In vitro cultures of cancer cells showed that FIT‐277 induced strong cell‐cell contact. Immunoblotting analysis showed that FTI‐277 increased E‐cadherin/catenin (α, β and γ) expression and strongly stabilized E‐cadherin/catenin with the actin cytoskeleton. Northern blotting studies indicated that the observed increase in the E‐cadherin/catenin protein content was due to increased expression of their genes. After inoculation of the spleens of mice with severe combined immunodeficiency (SCID) with cancer cells, FTI‐277 treatment for 3 weeks markedly reduced splenic primary tumor growth and the rate of liver metastasis compared with control counterparts. Our data demonstrate that FTI‐277 can activate functioning of the E‐cadherin‐mediated cell adhesion system, which is associated with suppression of cancer cell metastasis. Therefore, selective inhibition of Ras activation may be useful for preventing cancer metastasis. Blackwell Publishing Ltd 2002-09 /pmc/articles/PMC5927130/ /pubmed/12359056 http://dx.doi.org/10.1111/j.1349-7006.2002.tb02479.x Text en
spellingShingle Article
Nam, Jeong‐Seok
Ino, Yoshinori
Sakamoto, Michiie
Hirohashi, Setsuo
Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis
title Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis
title_full Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis
title_fullStr Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis
title_full_unstemmed Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis
title_short Ras Farnesylation Inhibitor FTI‐277 Restores the E‐Cadherin/Catenin Cell Adhesion System in Human Cancer Cells and Reduces Cancer Metastasis
title_sort ras farnesylation inhibitor fti‐277 restores the e‐cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927130/
https://www.ncbi.nlm.nih.gov/pubmed/12359056
http://dx.doi.org/10.1111/j.1349-7006.2002.tb02479.x
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