[Oncogenic activation of p21ras or pp60c-src in human colonic Caco-2 cells induces post-translation alterations of syndecan-1].
The protein encoded by ras and src protooncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study, we investigated the effect of oncogenic p21ras and Py-MT/pp60c-src on the synthesis of syndecan-1, a membrane anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells transfected with an activated (Val-12) human Ha-ras gene or the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. As compared to control vector-transfected Caco-2 cells, both oncogene-transfected cells exhibited: (1) a decrease in syndecan-1 specific activity; (2) a decrease in size and sulfation of syndecan-1 ectodomain glycosaminoglycan side chains; and (3) an active heparanase specifically degrading the heparan sulfate chains. In conclusion, the tumorigenic progression induced by oncogenic p21ras or Py-MT/pp60c-src is associated with marked alterations of syndecan-1 at the post-translational level.
Lévy
P
P
INSERM U. 402, Faculté de médecine Saint-Antoine, Paris, France.
Munier
A
A
Baron-Delage
S
S
Chastre
E
E
Gespach
C
C
Capeau
J
J
Cherqui
G
G
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D018938:Caco-2 Cells; D002809:Chondroitin Sulfates / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D018014:Gene Transfer Techniques; D011905:Genes, ras / Q000235:genetics; D005966:Glucuronidase; D006026:Glycoside Hydrolases / Q000378:metabolism; D006497:Heparan Sulfate / Q000032:analysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D000099175:Heparanase
D000952:Antigens, Polyomavirus Transforming; D002809:Chondroitin Sulfates; D005966:Glucuronidase; D006026:Glycoside Hydrolases; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D015689:Oncogene Protein p21(ras); D015688:Oncogene Protein pp60(v-src); D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; D000099175:Heparanase; C508241:SDC1 protein, human