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Biochem Biophys Res Commun. 2008 Dec 12;377(2):474-478. doi: 10.1016/j.bbrc.2008.09.138. Epub 2008 Oct 11.

Midkine promotes tetraspanin-integrin interaction and induces FAK-Stat1alpha pathway contributing to migration/invasiveness of human head and neck squamous cell carcinoma cells.

Author information

1
Department of Dermatology, The Johns Hopkins University School of Medicine, David H. Koch Cancer Research Building, Rm 2M05, 1550 Orleans Street, Baltimore, MD 21231, USA.
2
Department of Dermatology, The Johns Hopkins University School of Medicine, David H. Koch Cancer Research Building, Rm 2M05, 1550 Orleans Street, Baltimore, MD 21231, USA. Electronic address: eratovi1@jhmi.edu.

Abstract

The heparin-binding growth factor, MK, promoting tumorigenesis and survival was found to associate with alpha6beta1 integrins. We showed for the first time that MK interacted with TSPAN1 and facilitated the association between TSPAN1 and integrin alpha6beta1 proteins in head and neck squamous cell carcinoma (HNSCC) cells. We found that MK mediated an integrin-dependent tyrosine phosphorylation of FAK and activation of paxillin and Stat1alpha pathways. As result, downstream target genes implicated in cell migration and invasiveness (e.g. MMP-2 and MMP-26) were overexpressed. We observed that RNAi silencing of the critical signaling intermediates led to decrease of MK-induced migration/invasiveness of HNSCC cells. The major finding of this study is a novel MK-triggered signaling mechanism implicated in migration and invasiveness of HNSCC cells.

PMID:
18851943
DOI:
10.1016/j.bbrc.2008.09.138
[Indexed for MEDLINE]

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