Ras farnesylation inhibitor FTI-277 restores the E-cadherin/catenin cell adhesion system in human cancer cells and reduces cancer metastasis

Jeong Seok Nam, Yoshinori Ino, Michiie Sakamoto, Setsuo Hirohashi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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 FTI-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.

Original languageEnglish
Pages (from-to)1020-1028
Number of pages9
JournalJapanese Journal of Cancer Research
Volume93
Issue number9
Publication statusPublished - 2002 Sep 1
Externally publishedYes

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Prenylation
Catenins
Cadherins
Cell Adhesion
Neoplasm Metastasis
Neoplasms
Severe Combined Immunodeficiency
Cell Aggregation
FTI 277
Liver Neoplasms
Actin Cytoskeleton
Immunoblotting
Northern Blotting
Colonic Neoplasms
Spleen
Cell Culture Techniques
Breast Neoplasms
Gene Expression
Liver

Keywords

  • Catenin
  • E-Cadherin
  • FTI-277
  • Metastasis
  • Ras

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

In: Japanese Journal of Cancer Research, Vol. 93, No. 9, 01.09.2002, p. 1020-1028.

Research output: Contribution to journalArticle

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