Abnormal glycosylation and altered Golgi structure in colorectal cancer: dependence on intra-Golgi pH.
Abnormal glycosylation of cellular glycoconjugates is a common phenotypic change in many human tumors. Here, we explore the possibility that an altered Golgi pH may also be responsible for these cancer-associated glycosylation abnormalities. We show that a mere dissipation of the acidic Golgi pH results both in increased expression of some cancer-associated carbohydrate antigens and in structural disorganization of the Golgi apparatus in otherwise normally glycosylating cells. pH dependence of these alterations was confirmed by showing that an acidification-defective breast cancer cell line (MCF-7) also displayed a fragmented Golgi apparatus, whereas the Golgi apparatus was structurally normal in its acidification-competent subline (MCF-7/AdrR). Acidification competence was also found to rescue normal glycosylation potential in MCF-7/AdrR cells. Finally, we show that abnormal glycosylation is also accompanied by similar structural disorganization and fragmentation of the Golgi apparatus in colorectal cancer cells in vitro and in vivo. These results suggest that an inappropriate Golgi pH may indeed be responsible for the abnormal Golgi structure and lowered glycosylation potential of the Golgi apparatus in malignant cells.
Kellokumpu
Sakari
S
Department of Biochemistry, University of Oulu, P.O. Box 3000, FIN-90014, Oulu, Finland. sakari.kellokumpu@oulu.fi
Sormunen
Raija
R
Kellokumpu
Ilmo
I
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D019556:COS Cells; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure*; D005260:Female; D006031:Glycosylation; D006056:Golgi Apparatus / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008854:Microscopy, Electron; D051381:Rats; D014407:Tumor Cells, Cultured
D015295:Antigens, Tumor-Associated, Carbohydrate