The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC.
Oncogene
; 28(6): 792-802, 2009 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-19060919
ABSTRACT
Ezrin is a member of the ERM (ezrin, radixin, moesin) protein family and links F-actin to the cell membrane following phosphorylation. Ezrin has been associated with tumor progression and metastasis in several cancers including the pediatric solid tumors, osteosarcoma and rhabdomyosarcoma. In this study, we were surprised to find that ezrin was not constitutively phosphorylated but rather was dynamically regulated during metastatic progression in osteosarcoma. Metastatic osteosarcoma cells expressed phosphorylated ERM early after their arrival in the lung, and then late in progression, only at the invasive front of larger metastatic lesions. To pursue mechanisms for this regulation, we found that inhibitors of PKC (protein kinase C) blocked phosphorylation of ezrin, and that ezrin coimmunoprecipitated in cells with PKCalpha, PKCiota and PKCgamma. Furthermore, phosphorylated forms of ezrin and PKC had identical expression patterns at the invasive front of pulmonary metastatic lesions in murine and human patient samples. Finally, we showed that the promigratory effects of PKC were linked to ezrin phosphorylation. These data are the first to suggest a dynamic regulation of ezrin phosphorylation during metastasis and to connect the PKC family members with this regulation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Citoesqueleto
/
Proteína Quinase C
/
Osteossarcoma
/
Regulação Neoplásica da Expressão Gênica
/
Actinas
/
Proteínas do Citoesqueleto
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article