J Cancer 2017; 8(17):3480-3489. doi:10.7150/jca.21241

Research Paper

Restoration of KLF4 Inhibits Invasion and Metastases of Lung Adenocarcinoma through Suppressing MMP2

Shaoli Li1, Lixia Huang1, Jincui Gu1, Jian Wu1, Weijun Ou2, Jinglun Feng1, Baomo Liu1, Xiaoxian Cui1, Yanbin Zhou1✉

1. Department of Respiratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
2. Center of Organ Transplantation, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Abstract

Background: KLF4 is a zin-finger transcription factor that plays roles in differentiation, development, and proliferation. Recent studies show that KLF4 is involved in tumorigenesis and somatic cells reprogramming. Metastasis is the primary cause of death in patients with lung cancer, and its biological mechanisms are poorly understood.

Goals: In this study, we aim to explore the expression pattern and biological function of KLF4 in lung adenocarcinoma.

Methods: We determined KLF4 in lung adenocarcinoma tissue and cell lines, using immunohistochemistry and western blotting. And we further analyzed the correlation between KLF4 expression and clinicopathologic parameters. We restored KLF4 expression and studied its effect on lung adenocarcinoma cells in vivo and in vitro. Luciferase assay was used to study impact of KLF4 on activity of MMP2 promoter.

Results: KLF4 is dramatically down-regulated in lung adenocarcinoma tissue and cell lines. Promoter methylation contributes to the down-regulation of KLF4. Down-regulation of KLF4 in lung adenocarcinoma tissue is significantly associated with reduced survival time. Restoration of KLF4 inhibits migration and invasion of lung adenocarcinoma cells in vitro. Metastases to lungs significantly decrease in mice intravenously injected with tumor cells overexpressing KLF4. KLF4 inhibits invasion and metastasis via suppressing MMP2 promoter activity.

Conclusion: The ability of KLF4 to inhibit migration, invasion, and metastasis of lung tumor cells indicates a potential role of KLF4 as therapeutic target in lung adenocarcinoma. KLF4 might be utilized as a favorable biomarker for prognosis of lung adenocarcinoma patients.

Keywords: Krüppel-like factor, GKLF, Invasion, Metastasis, MMP2

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How to cite this article:
Li S, Huang L, Gu J, Wu J, Ou W, Feng J, Liu B, Cui X, Zhou Y. Restoration of KLF4 Inhibits Invasion and Metastases of Lung Adenocarcinoma through Suppressing MMP2. J Cancer 2017; 8(17):3480-3489. doi:10.7150/jca.21241. Available from http://www.jcancer.org/v08p3480.htm