Abstract
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.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport*
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Adenoviridae / genetics
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Anoikis*
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Apoptosis Regulatory Proteins
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Breast Neoplasms / enzymology*
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Female
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Genes, Tumor Suppressor
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Genetic Vectors
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Humans
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MAP Kinase Signaling System
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Proteins / genetics
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Proteins / physiology*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-akt
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Signal Transduction*
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Transfection
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Tumor Cells, Cultured
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Tumor Suppressor Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Apoptosis Regulatory Proteins
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DAB2 protein, human
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Proteins
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Proto-Oncogene Proteins
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Tumor Suppressor Proteins
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integrin-linked kinase
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt