Oncotarget

Research Papers:

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

Hyo-Jong Lee, Ji-Sun Lee, Su Jung Hwang and Ho-Young Lee _

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Oncotarget. 2015; 6:15150-15163. https://doi.org/10.18632/oncotarget.3825

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Abstract

Hyo-Jong Lee1,2,3, Ji-Sun Lee4, Su Jung Hwang1 and Ho-Young Lee4

1 College of Pharmacy, Inje University, Gimhae, Gyungnam, Republic of Korea

2 u-Healthcare and Anti-aging Research Center (u-HARC), Inje University, Gimhae, Republic of Korea

3 Biohealth Products Research Center (BPRC), Inje University, Gimhae, Republic of Korea

4 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea

Correspondence to:

Ho-Young Lee, email:

Keywords: IGFBP-3, IGF-1, integrin, cell adhesion, AP-1, angiogenesis

Received: December 18, 2014 Accepted: March 26, 2015 Published: April 14, 2015

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 β4, 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 β4 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 β4 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.


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