title: Regulation of CD44 expression and focal adhesion by Golgi phosphatidylinositol 4-phosphate in breast cancer.
abstract: 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 IIIβ 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.
authors.affiliation: Division of Biochemistry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ijuin
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
authors.affiliation: Division of Membrane Biology, Biosignal Research Center, Kobe University, Kobe, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Tokuda
authors.affiliation: Division of Membrane Biology, Biosignal Research Center, Kobe University, Kobe, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000172:deficiency / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000235:genetics; D010766:Phosphorylation; D016596:Vinculin / Q000378:metabolism; D000099149:Ezrin
chemical_list: D019870:1-Phosphatidylinositol 4-Kinase; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D010744:Phosphoric Monoester Hydrolases; D016596:Vinculin; D000099149:Ezrin; C416669:Sac1 protein, mammalian; C037178:phosphatidylinositol 4-phosphate; C071776:radixin
keywords: Breast cancer; CD44; SAC1; focal adhesion; phosphatidylinositol-4-monophosphate