Phosphatidylinositol 4-phosphate in the Golgi apparatus regulates cell-cell adhesion and invasive cell migration in human breast cancer.
Downregulation of cell-cell adhesion and upregulation of cell migration play critical roles in the conversion of benign tumors to aggressive invasive cancers. In this study, we show that changes in cell-cell adhesion and cancer cell migration/invasion capacity depend on the level of phosphatidylinositol 4-phosphate [PI(4)P] in the Golgi apparatus in breast cancer cells. Attenuating SAC1, a PI(4)P phosphatase localized in the Golgi apparatus, resulted in decreased cell-cell adhesion and increased cell migration in weakly invasive cells. In contrast, silencing phosphatidylinositol 4-kinase IIIβ, which generates PI(4)P in the Golgi apparatus, increased cell-cell adhesion and decreased invasion in highly invasive cells. Furthermore, a PI(4)P effector, Golgi phosphoprotein 3, was found to be involved in the generation of these phenotypes in a manner that depends on its PI(4)P-binding ability. Our results provide a new model for breast cancer cell progression in which progression is controlled by PI(4)P levels in the Golgi apparatus.
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Emi
E
Tokuda
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Toshiki
T
Itoh
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Junya
J
Hasegawa
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Takeshi
T
Ijuin
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Yukiko
Y
Takeuchi
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Yasuhiro
Y
Irino
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan.
Miki
M
Fukumoto
Authors' Affiliations: Integrated Center for Mass Spectrometry; Division of Membrane Biology; and Department of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, Japan takenawa@med.kobe-u.ac.jp.
Tadaomi
T
Takenawa
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding
D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D017853:Phosphotransferases (Alcohol Group Acceptor); C429024:GOLPH3 protein, human; C037178:phosphatidylinositol 4-phosphate; C581087:PI4KB protein, human