Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer.
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.
Shibata
Tatsuhiro
T
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kokubu
Akiko
A
Sekine
Shigeki
S
Kanai
Yae
Y
Hirohashi
Setsuo
S
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics*; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology*; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D019000:Phosphotyrosine; D000095002:Delta Catenin; C000722347:CTNND1 protein, human