POU5F1 Enhances the Invasiveness of Cancer Stem-Like Cells in Lung Adenocarcinoma by Upregulation of MMP-2 Expression

Yan-hong Xin, Bai-shi-jiao Bian, Xiao-jun Yang, Wei Cui, Hong-juan Cui, You-hong Cui, Xia Zhang, Chuan Xu and Xiu-wu Bian

PLOS ONE, 2013, vol. 8, issue 12, 1-8

Abstract: Lung cancer is the leading cause of cancer-related human deaths. Exploration of the mechanisms underlying the metastasis of cancer stem-like cells (CSLCs) will open new avenues in lung cancer diagnosis and therapy. Here, we demonstrated that CSLCs-derived from lung adenocarcinoma (LAC) cells displayed highly invasive and migratory capabilities via expressing high levels of POU5F1 and MMP-2. We found that POU5F1 directly regulated MMP-2 transcription via interaction with the promoter of MMP-2. POU5F1 knockdown in LACSLCs reduced MMP-2 protein abundance, leading to inhibition of the cell invasion, migration and tumorigenesis potentials of LAC cells. Clinically, aberrantly high expressions of POU5F1 and MMP-2 were inversely correlated with the survival of LAC patients, and the double-positive POU5F1 and MMP-2 showed the worst prediction for the patient’s poor survival. These results indicate that POU5F1 can bind to the MMP-2 promoter for the degradation of surrounding extracellular matrix, and therefore promote invasive and migratory capabilities of LACSLCs. Moreover, our data implicate that the pathological detection of the double-positive expressions for POU5F1 and MMP-2 will be useful as diagnostic and prognostic biomarkers in LAC to advance anti-metastasis therapy.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0083373

DOI: 10.1371/journal.pone.0083373

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