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Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrin ?4 expression.

ABSTRACT: We previously reported that IGF binding protein-3 (IGFBP-3), a major IGF-binding protein in human serum, regulates angiogenic activities of human head and neck squamous cell carcinoma (HNSCC) cells and human umbilical vein endothelial cells (HUVECs) through IGF-dependent and IGF-independent mechanisms. However, the role of IGFBP-3 in cell adhesion is largely unknown. We demonstrate here that IGFBP-3 inhibits the adhesion of HNSCC cells and HUVECs to the extracellular matrix (ECM). IGFBP-3 reduced transcription of a variety of integrins, especially integrin ?4, and suppressed phosphorylation of focal adhesion kinase (FAK) and Src in these cells through both IGF-dependent and IGF-independent pathways. IGFBP-3 was found to suppress the transcription of c-fos and c-jun and the activity of AP1 transcription factor. The regulatory effect of IGFBP-3 on integrin ?4 transcription was attenuated by blocking c-jun and c-fos gene expression via siRNA transfection. Taken together, our data show that IGFBP-3 has IGF-dependent and -independent inhibitory effects on intracellular adhesion signaling in HNSCC and HUVECs through its ability to block c-jun and c-fos transcription and thus AP-1-mediated integrin ?4 transcription. Collectively, our data suggest that IGFPB-3 may be an effective cancer therapeutic agent by blocking integrin-mediated adhesive activity of tumor and vascular endothelial cells.

SUBMITTER: Lee HJ

PROVIDER: S-EPMC4558142 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrin β4 expression.

Lee Hyo-Jong HJ Lee Ji-Sun JS Hwang Su Jung SJ Lee Ho-Young HY

Oncotarget 20150601 17

We previously reported that IGF binding protein-3 (IGFBP-3), a major IGF-binding protein in human serum, regulates angiogenic activities of human head and neck squamous cell carcinoma (HNSCC) cells and human umbilical vein endothelial cells (HUVECs) through IGF-dependent and IGF-independent mechanisms. However, the role of IGFBP-3 in cell adhesion is largely unknown. We demonstrate here that IGFBP-3 inhibits the adhesion of HNSCC cells and HUVECs to the extracellular matrix (ECM). IGFBP-3 reduce ...[more]

PMID: 25945837

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Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrin ?4 expression.

Publications

Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrin β4 expression.

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