Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer

Tatsuhiro Shibata, Akiko Kokubu, Shigeki Sekine, Yae Kanai, Setsuo Hirohashi

Research output: Contribution to journalArticle

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Abstract

In a search for signaling molecules that act downstream of E-cadherin inactivation in cancer, we examined the expression and localization of E-cadherin-associated proteins in lobular carcinoma, in which the E-cadherin gene is frequently inactivated, and found that E-cadherin down-regulation correlated with the cytoplasmic localization of p120ctn. Similar cytoplasmic localization of p120ctn and growth factor-induced accumulation of tyrosine-phosphorylated p120ctn in the protrusive domain were observed in E-cadherin-deficient breast cancer cells. Down-regulation of endogenous p120ctn by RNA interference promoted stress fiber formation and induced a flattened morphology with an increase of Rho-GTPase activity; it also reduced the development of membranous protrusions and migratory activity in E-cadherin-deficient breast cancer cells. Inactivation of E-cadherin in cancer cells is associated with the conversion from epithelial to mesenchymal phenotype, which also occurs in physiological conditions such as developmental processes. Cytoplasmic localization of p120ctn accompanied by E-cadherin down-regulation was observed in mesoderm cells that had undergone epithelial-mesenchymal transition during early mouse embryogenesis. Collectively, our results suggest that cytoplasmic p120ctn may contribute to the invasive phenotype of E-cadherin-deficient breast cancer cells.

Original languageEnglish
Pages (from-to)2269-2278
Number of pages10
JournalAmerican Journal of Pathology
Volume164
Issue number6
Publication statusPublished - 2004 Jun
Externally publishedYes

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Cadherins
Breast Neoplasms
Phenotype
Down-Regulation
Lobular Carcinoma
delta catenin
Stress Fibers
rho GTP-Binding Proteins
Epithelial-Mesenchymal Transition
Mesoderm
RNA Interference
Embryonic Development
Tyrosine
Neoplasms
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer. / Shibata, Tatsuhiro; Kokubu, Akiko; Sekine, Shigeki; Kanai, Yae; Hirohashi, Setsuo.

In: American Journal of Pathology, Vol. 164, No. 6, 06.2004, p. 2269-2278.

Research output: Contribution to journalArticle

Shibata, T, Kokubu, A, Sekine, S, Kanai, Y & Hirohashi, S 2004, 'Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer', American Journal of Pathology, vol. 164, no. 6, pp. 2269-2278.
Shibata, Tatsuhiro ; Kokubu, Akiko ; Sekine, Shigeki ; Kanai, Yae ; Hirohashi, Setsuo. / Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer. In: American Journal of Pathology. 2004 ; Vol. 164, No. 6. pp. 2269-2278.
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