¹The Department of Cell Research and Immunology, Tel Aviv, Israel

²The Ela Kodesz Institute for Research on Cancer Development and Prevention, Tel Aviv University, Tel Aviv 69978, Israel

³Department of Applied and Experimental Oncology, Institute for Cancer Research, University of Vienna, Vienna, Austria

Correspondence to: I Yron, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel; E-mail: ilanayr@post.tau.ac.il

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.

Oncogene (2002) 21, 3969-3977 doi:10.1038/sj.onc.1205472

melanoma; anchorage independence; integrins; FAK; phosphorylation; cytoskeleton