Oncotarget

Research Papers:

DACH1 inhibits lung adenocarcinoma invasion and tumor growth by repressing CXCL5 signaling

Na Han, Xun Yuan, Hua Wu, Hanxiao Xu, Qian Chu, Mingzhou Guo, Shiying Yu, Yuan Chen and Kongming Wu _

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Oncotarget. 2015; 6:5877-5888. https://doi.org/10.18632/oncotarget.3463

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Abstract

Na Han1, Xun Yuan1, Hua Wu1, Hanxiao Xu1, Qian Chu1, Mingzhou Guo2, Shiying Yu1, Yuan Chen1 and Kongming Wu1

1 Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China

2 Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, P.R. China

Correspondence to:

Kongming Wu, email:

Keywords: DACH1, Non-small cell lung cancer, invasion, tumor growth, CXCL5

Received: October 16, 2014 Accepted: January 22, 2015 Published: February 28, 2015

Abstract

Whole-genome and transcriptome sequencing of non-small cell lung cancer (NSCLC) identified that DACH1, is a human homolog of drosophila gene dac, is involved in NSCLC. Here we showed that expression of DACH1 was significantly decreased in human NSCLC tissues and DACH1 abundance was inversely correlated with tumor stages and grades. Restoration of DACH1 expression in NSCLC cells significantly reduced cellular proliferation, clone formation, migration and invasion in vitro, as well as tumor growth in vivo. Unbiased screen and functional study suggested that DACH1 mediated effects were dependent in part on suppression of CXCL5. There was an inverse correlation between DACH1 mRNA levels and CXCL5 in both lung cancer cell lines and human NSCLC tissues. Kaplan-Mier analysis of human NSCLC samples demonstrated that high DACH1 mRNA levels predicted favorable prognosis for relapse-free and overall survival. In agreement, high CXCL5 expression predicted a worse prognosis for survival.


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