The integrin-linked kinase (ILK) suppresses anoikis

Citation
S. Attwell et al., The integrin-linked kinase (ILK) suppresses anoikis, ONCOGENE, 19(33), 2000, pp. 3811-3815
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
19
Issue
33
Year of publication
2000
Pages
3811 - 3815
Database
ISI
SICI code
0950-9232(20000803)19:33<3811:TIK(SA>2.0.ZU;2-C
Abstract
Disruption of integrin-extracellular matrix interactions in normal epitheli al cells induces apoptosis, a process termed anoikis, Reduced sensitivity t o anoikis appears to be an important hallmark of oncogenic transformation, particularly in the process of metastasis, Several pathways have been impli cated in the suppression of anoikis, however, the events which take place p roximal to the integrin receptors remain unclear. Integrin-linked kinase (I LK) is an integrin-interacting protein kinase which has been identified as a potential PDK-2, as it is capable of phosphorylating PKB/Akt on Ser-473, and stimulating its activity, Here, we show that ILK activity is stimulated upon adhesion of SCP2 mouse mammary epithelial cells to fibronectin, and i nhibited in suspended cells. Overexpression of ILK in the anoikis-sensitive SCP2 cells results in a profound inhibition of anoikis, as determined by a nnexin V binding and activation of caspases 8 and 3, This effect is reversi ble by the transfection and expression of a dominant-negative, kinase defic ient ILK (ILK KD), as well as by a dominant negative PKB/Akt (PKB AAA). On the other hand, transfection of a dominant negative form of FAK (FRNK) fail ed to reverse the suppression of anoikis by ILK, Furthermore, inhibition of ILK activity induced anoikis in tno anoikis-resistant human breast cancer cell lines. These findings suggest that ILK plays a major role in the suppr ession of anoikis.