Hyperphosphorylated cortactin in cancer cells plays an inhibitory role in cell motility.
Cortactin is frequently overexpressed in cancer cells, and changes of the levels of its tyrosine phosphorylation have been observed in several cancer cells. However, how the expression level and phosphorylation state of cortactin would influence the ultimate cellular function of cancer cells is unknown. In this study, we analyzed the role of cortactin in gastric and breast cancer cell lines using RNA interference technique and found that knockdown of cortactin inhibited cell migration in a subset of gastric cancer cells with a lower level of its tyrosine phosphorylation, whereas it greatly enhanced cell migration and increased tyrosine phosphorylation of p130Cas in other subsets of cells with hyperphosphorylated cortactin. Consistent results were obtained when hyperphosphorylation of cortactin was induced in MCF7 breast cancer cells by expressing Fyn tyrosine kinase. Additionally, immunostaining analysis showed that knockdown of hyperphosphorylated cortactin resulted in the recruitment of p130Cas to focal adhesions. These results suggest that cortactin hyperphosphorylation suppresses cell migration possibly through the inhibition of membrane localization and tyrosine phosphorylation of p130Cas.
Jia
Lin
L
National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
Uekita
Takamasa
T
Sakai
Ryuichi
R
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002999:Clone Cells; D051356:Cortactin / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
D051356:Cortactin; D050719:Crk-Associated Substrate Protein; D034741:RNA, Small Interfering; D019000:Phosphotyrosine