Integrin-linked kinase: a hypoxia-induced anti-apoptotic factor exploited by cancer cells.
Based on cDNA microarray results, integrin-linked kinase (ILK) emerged as an interesting candidate in hypoxia-mediated survival mechanisms employed by cancer cells. This notion was confirmed here by the following observations: the 5' promoter region of the ilk gene contains hypoxia responsive elements (HRE) that bind hypoxia-inducible factor (HIF) transcription factor complexes and drive HRE-luciferase gene expression in reporter assays; ILK protein and kinase activity are induced following hypoxia; downstream targets of ILK signaling are induced following hypoxia treatment; inhibition of ILK leads to increased apoptosis; and HIF and ILK are co-localized within human cancer tissues. The identification of ILK as a player in hypoxia survival signaling employed by cancer cells further validates ILK as a unique target for cancer therapy.
Abboud
Elizabeth R
ER
Molecular and Cellular Biology Program, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Coffelt
Seth B
SB
Figueroa
Yanira G
YG
Zwezdaryk
Kevin J
KJ
Nelson
Anne B
AB
Sullivan
Deborah E
DE
Morris
Cindy B
CB
Tang
Yan
Y
Beckman
Barbara S
BS
Scandurro
Aline B
AB
D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology; D008113:Liver Neoplasms; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D000099200:Scaffold Protein ILK
D004273:DNA, Neoplasm; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK