RESUMO
CD44, a transmembrane receptor, is expressed in the standard or variant form and plays a critical role in tumor progression and metastasis. This protein regulates cell adhesion and migration in breast cancer cells. We previously reported that phosphatidylinositol-4-phosphate (PI(4)P) at the Golgi regulates cell migration and invasion in breast cancer cell lines. In this study, we showed that an increase in PI(4)P levels at the Golgi by knockdown of PI(4)P phosphatase SAC1 increased the expression of standard CD44, variant CD44, and ezrin/radixin phosphorylation and enhanced the formation of focal adhesions mediated by CD44 and ezrin/radixin in MCF7 and SK-BR-3 cells. In contrast, knockdown of PI 4-kinase IIIß in highly invasive MDA-MB-231 cells decreased these factors. These results suggest that SAC1 expression and PI(4)P at the Golgi are important in tumor progression and metastasis and are potential prognostic markers of breast cancers.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Adesões Focais/metabolismo , Complexo de Golgi/metabolismo , Receptores de Hialuronatos/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , 1-Fosfatidilinositol 4-Quinase/deficiência , 1-Fosfatidilinositol 4-Quinase/genética , Neoplasias da Mama/enzimologia , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/genética , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Monoéster Fosfórico Hidrolases/deficiência , Monoéster Fosfórico Hidrolases/genética , Fosforilação , Vinculina/metabolismoRESUMO
Phosphoinositides comprise a group of essential phospholipids that control a variety of cellular functions. In the case of the human malaria parasite Plasmodium falciparum, phosphoinositides have been shown to trigger exflagellation and to affect haemoglobin endocytosis and maturation of the parasite's digestive vacuole. A central enzyme in the formation of phosphoinositides is the phosphatidylinositol 4-kinase that catalyzes the production of phosphatidylinositol 4-phosphate from phosphatidylinositol. Here we have identified and characterized a phosphatidylinositol 4-kinase from P. falciparum. Our data show that the corresponding P. falciparum gene, termed PFE0485w, can functionally complement a yeast temperature-sensitive pik1 mutation. Our data add to the concept that P. falciparum maintains its own phospholipids biosynthesis pathway.
