Contributions of integrin-linked kinase to breast cancer metastasis and tumourigenesis.
Metastasis contributes to more than 90% of mortality in breast cancer. Critical stages in the development of aggressive breast cancer include growth of the primary tumours, and their abilities to spread to distant organs, colonize and establish an independent blood supply. The integrin family of cell adhesion receptors is essential to breast cancer progression. Furthermore, integrin-linked kinase can 'convert' localized breast cancer cells into invasive and metastatic cells. Upon stimulation by growth factors and chemokine ligands, integrin-linked kinase mediates the phosphorylation of Akt Ser473, and glycogen synthase kinase-3. The current notion is that overexpression of integrin-linked kinase resulted in an invasive, metastatic phenotype in several cancer model systems in vivo and in vitro, thus, implicating a role for integrin-linked kinase in oncogenic transformation, angiogenesis and metastasis. Here, we will review the role of integrin-linked kinase in breast cancer metastasis. Elucidation of signalling events important for breast tumour metastasis should provide insights into successful breast cancer therapies.
Hinton
Cimona V
CV
Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Avraham
Shalom
S
Avraham
Hava Karsenty
HK
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099200:Scaffold Protein ILK
D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D042461:Vascular Endothelial Growth Factor A; D000099200:Scaffold Protein ILK