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.
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.
Katayama
Hiroshi
H
Katayama Dermatology, 371-0024 Maebashi, Japan. kdermatology@jcom.home.ne.jp
Yamane
Yasuhiro
Y
Furukawa
Yusuke
Y
Kitagawa
Seiichi
S
Nakamura
Yukio
Y
Yoshino
Kaori
K
D017209:Apoptosis; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000097794:Kalinin