The focal adhesion kinase (P125FAK) is constitutively active in human malignant melanoma.
Malignant melanoma cells show high aggressiveness and metastatic potential. Tumor cells as they become more metastatic, gradually lose their dependence on both adhesion and serum. Thus, in the process of tumor progression cells undergo series of changes that allow them to adapt to different tissue milieu. This implies that during this process, points on the integrin pathway may become constitutively activated. In the present study we investigated the possible role of FAK, being one of the key members of the integrin-signaling pathway, in the multistep progression towards a malignant phenotype in human melanoma. In our study we show that in melanoma cells there is neither an increase in the amount of FAK nor in its phosphorylation capacity, but rather in its levels of constitutive activation. Indeed, in all melanoma cells tested and not in nevus and neuroblastoma cells, we observed various degrees of constitutive activation of FAK. Our results also suggest that FAK constitutive activation is regulated at least in part by the cytoskeleton, implying that steps along the integrin signaling pathway involving FAK could be among the oncogenic mechanisms that operate in melanoma and may account for the highly aggressive, anchorage independent phenotype of this tumor.
Kahana
Orlie
O
The Department of Cell Research and Immunology, Tel Aviv, Israel.
Micksche
Michael
M
Witz
Isaac P
IP
Yron
Ilana
I
D002448:Cell Adhesion; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism; D009508:Nevus, Pigmented / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D016023:Integrins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human