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Title of Journal: Mol Cell Biochem

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Abbravation: Molecular and Cellular Biochemistry

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Springer US

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DOI

10.1016/0022-3115(83)90296-9

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ISSN

1573-4919

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AP4 activates cell migration and EMT mediated by p

Authors: Shaopeng Chen SungKay Chiu
Publish Date: 2015/06/03
Volume: 407, Issue: 1-2, Pages: 57-68
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Abstract

Tumor metastasis is the primary cause of mortality in most cancer patients Before disassociation from the tumors most of malignant tumor cells undergo the epithelial–mesenchymal transition to break away from the adhesions between the cells and the surrounding extracellular matrix Recently activating enhancerbinding protein AP4 has been shown to be a mediator of EMT in colorectal cancer and high level of AP4 correlates with poor prognosis in cancer patients It has been found that AP4 upregulates the genes involved in EMT and cell proliferation in colorectal cancer cells and that the aggressive human breast cancer cells MDAMB231 are highly metastatic Therefore we tested the hypothesis that AP4 may also affect cell migration and EMT in this cell type Three different assays including the woundhealing assay the Boyden chamber assay and the cell tracking assay were employed to confirm that AP4 activated both cell migration and invasion Immunofluorescence staining and Western blot analysis revealed that the cells underwent EMT when AP4 was upregulated In contrast overexpression of dominantnegative AP4 lacking the DNAbinding domain inactivated the DNAbinding ability of endogenous AP4 and led to lower cell motility Furthermore we found that AP4 enhanced p53 expression at both transcriptional and translational levels Knockdown of p53 by siRNA significantly diminished the activation of cell migration by AP4 indicating that AP4 can regulate cell migration via the activity of p53

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