Research Papers:

Elevated AEG-1 expression in macrophages promotes hypopharyngeal cancer invasion through the STAT3-MMP-9 signaling pathway

Xiuxiu Liu, Zhenghua Lv, Jidong Zou, Xianfang Liu, Juke Ma, Chengtao Sun, Na Sa and Wei Xu _

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Oncotarget. 2016; 7:77244-77256. https://doi.org/10.18632/oncotarget.12886

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Xiuxiu Liu1,2,*, Zhenghua Lv1,*, Jidong Zou1, Xianfang Liu1,2, Juke Ma1, Chengtao Sun1, Na Sa1, Wei Xu1,2

1Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China

2Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China

*These authors contributed equally to this work

Correspondence to:

Wei Xu, email: [email protected]

Keywords: macrophages, cancer invasion, AEG-1, MMP-9, hypopharyngeal cancer

Received: July 11, 2016     Accepted: October 14, 2016     Published: October 25, 2016


Macrophages play a critical role in tumor invasion and metastasis, which remain major causes of mortality in patients with hypopharyngeal cancer. Here we investigate the effect of an oncogene, AEG-1 expressed in macrophages on the invasion of hypopharyngeal cancer cells. AEG-1 is more highly expressed in macrophages of human hypopharyngeal cancer samples compared with adjacent non-tumor controls. Using matrigel invasion assay system, THP-1-derived macrophages with forced AEG-1 overexpression enhance FaDu cell invasion whereas macrophages with AEG-1 silence inhibit. Matrix metalloproteinase 9 (MMP-9), which is important in tumor invasion and metastasis through degrading extracellular matrix, is up-reulated by AEG-1 partly through NF-κB p65 in macrophages. Intriguingly, macrophage AEG-1 also induces MMP-9 up-regulated expression in FaDu cells. Furthermore, macrophage AEG-1 activates signal transducer and activator of transcription 3 (STAT3) in FaDu cells, which is responsible for macrophage AEG-1-induced an increase in MMP-9 expression and invasion of FaDu cells. This is the first to demonstrate that macrophage AEG-1 promotes tumor invasion through up-regulation of MMP-9 in both macrophages and cancer cells. Thus, the results provide evidences that macrophage AEG-1 contributes to promotion of tumor invasion, and represents as a potential target in hypopharyngeal cancer therapy.

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