Essential roles of integrin-mediated signaling for the enhancement of malignant properties of melanomas based on the expression of GD3.
We reported that ganglioside GD3 enhances cell proliferation and invasion of melanomas causing stronger tyrosine-phosphorylation of p130Cas and paxillin after stimulation with fetal calf serum. Besides signals via growth factor/receptor, adhesion signals via integrin might be also enhanced by GD3. Here, roles of integrin-mediated signaling in the cell proliferation and invasion, and in the activation of adaptor molecules were examined, showing that integrin was also important for the cell growth and invasion. p130Cas and paxillin underwent stronger tyrosine-phosphorylation in GD3+ cells than in GD3- cells during the adhesion in the absence of serum. On the other hand, no proteins underwent tyrosine phosphorylation in GD3+ and GD3- cells in a suspension state when stimulated with fetal calf serum. These results suggested that integrin-mediated signaling is essential in the effects of GD3 on the malignant properties of melanomas. Co-localization of GD3 and integrin at the focal adhesion supported these results.
Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Aichi, Japan.
Yuki
Y
Ohkawa
Sayaka
S
Miyazaki
Maiko
M
Miyata
Kazunori
K
Hamamura
Koichi
K
Furukawa
Keiko
K
Furukawa
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
D050719:Crk-Associated Substrate Protein; D005732:Gangliosides; D019012:Integrin beta1; D051419:Paxillin; C026226:ganglioside, GD3