Monosialyl-Gb5 organized with cSrc and FAK in GEM of human breast carcinoma MCF-7 cells defines their invasive properties.
Two human mammary carcinoma cell variants, MCF-7/AZ and MCF-7/6, show the same composition in their glycosphingolipid-enriched microdomain (GEM) with regard to globo-series structures Gb3, Gb4, Gb5, monosialyl-Gb5, GM2, and cSrc and FAK. Both variants are non-invasive into collagen gel layer, and showed similar motility in wound migration assay. Whereas invasiveness and motility of MCF-7/AZ cells were enhanced greatly by treatment with mAb RM1 directed to monosialyl-Gb5, the same RM1 treatment had no effect on MCF-7/6. cSrc and FAK of MCF-7/AZ, but not MCF-7/6, were activated by RM1 treatment. Thus, malignancy of MCF-7 is highly dependent on monosialyl-Gb5, and its activation of cSrc and FAK in GEM.
Steelant
Wim F
WF
Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122-4327, USA.
Kawakami
Yasushi
Y
Ito
Akihiro
A
Handa
Kazuko
K
Bruyneel
Erik A
EA
Mareel
Marc
M
Hakomori
Senitiroh
S
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis; D002460:Cell Line; D002465:Cell Movement; D002855:Chromatography, Thin Layer; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*; D060245:Tetraspanin 29; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D019061:src-Family Kinases / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D013107:Sphingolipids; D060245:Tetraspanin 29; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D019061:src-Family Kinases