Paediatrics Publications

Title

Identification of Dermcidin as a novel binding protein of Nck1 and characterization of its role in promoting cell migration

Document Type

Article

Publication Date

6-1-2011

Journal

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volume

1812

Issue

6

First Page

703

Last Page

710

URL with Digital Object Identifier

10.1016/j.bbadis.2011.03.004

Abstract

A distinct feature of hepatocellular carcinoma (HCC) is the tendency of tumor cells to disperse throughout the liver. Nck family adaptor proteins function to couple tyrosine phosphorylation signals to regulate actin cytoskeletal reorganization that leads to cell motility. In order to explore the role of Nck in HCC development, we performed GST pull-down assay using the SH2 domain of Nck1 as bait. The resulting precipitates were separated by 2-DE. Mass spectrometry analysis revealed a group of Nck1 SH2 domain-binding proteins that were differentially expressed in HCC. One of these proteins, dermcidin (DCD), and its interaction with Nck1, was further validated in vitro. GST pull-down assay revealed that Nck1 SH2 domain binds to the phosphotyrosine residue at position 20 (Y20) of the DCD. Pervandate treatment significantly enhanced the interaction between DCD and Nck1. Moreover, we demonstrated that forced expression of DCD could activate Rac1 and Cdc42 and promoted cell migration. Taken together, these data suggest a role of DCD in tumor metastasis. © 2011 Elsevier B.V.

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