Activation of Focal Adhesion Kinase in Detached Human Epidermal Cancer Cells and Their Long-term Survival Might be Associated with Cell Surface Expression of Laminin-5

Abstract

While normal epithelial cells are anchorage-dependent, cancer cells are anchorage-independent. To elucidate the mechanism underlying the anchorage-independence of cancer cells, we cultured detached cells in medium containing elastase. Detached human epidermal cancer cells (DJM-1) survived for at least 3 weeks and focal adhesion kinase was still phosphorylated. In contrast, most detached keratinocytes underwent rapid apoptosis and focal adhesion kinase was not phosphorylated while the cells were alive. Thus, discontinuation of the phosphorylation of focal adhesion kinase preceded cell death. Immunostaining showed laminin-5 expression on the surface of detached DJM-1 cells, but not on detached keratinocytes. Receptors for laminin-5 (i.e. integrins) were detected on both detached DJM-1 cells and keratinocytes. Laminins are secreted proteins, so we speculated that laminin-5 adhered to the surface of secreting DJM-1 cells via integrins and evoked activation of focal adhesion kinase, with the resultant signalling cascade promoting cellular survival. If this hypothesis is correct, cell surface expression of laminin-5 may be used to explain the characteristics of cancer, immortality, tumour formation, metastasis and angiogenesis.