DOC-2/hDab-2 inhibits ILK activity and induces anoikis in breast cancer cells through an Akt-independent pathway.
DOC-2/hDab-2 was identified due to the loss of its expression in primary ovarian cancer cells. It is believed that loss of DOC-2/hDab-2 expression is one of the early events of ovarian malignancy. These results suggest a function of DOC-2/hDab-2 as a tumor suppressor. However, it is not clear how DOC-2/hDab-2 negatively regulates cancer cell growth. In this report, we demonstrate that DOC-2/hDab-2 expression in breast cancer cells resulted in sensitivity to suspension-induced cell death (anoikis). This event was associated with the down-regulation of the integrin-linked kinase (ILK) activity. Since ILK is a key factor in regulating the cellular signaling in responding to the extracellular signals through adhesion molecules like integrins, our results indicate that DOC-2/hDab-2 may prevent tumor growth and invasion by modulating the anti-apoptotic ILK pathway.
Wang
S C
SC
Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Makino
K
K
Xia
W
W
Kim
J S
JS
Im
S A
SA
Peng
H
H
Mok
S C
SC
Singletary
S E
SE
Hung
M C
MC
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000256:Adenoviridae / Q000235:genetics; D023102:Anoikis; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006801:Humans; D020935:MAP Kinase Signaling System; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000099200:Scaffold Protein ILK
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; D000099200:Scaffold Protein ILK; C102885:DAB2 protein, human; C494918:AKT1 protein, human