Reciprocal activation between MMP-8 and TGF-β1 stimulates EMT and malignant progression of hepatocellular carcinoma

被引:87
作者
Qin, Guihui [1 ]
Luo, Min [1 ]
Chen, Junze [2 ]
Dang, Yiwu [3 ]
Chen, Gang [3 ]
Li, Li [4 ]
Zeng, Jing [5 ]
Lu, Yi [6 ]
Yang, Jie [1 ]
机构
[1] Guangxi Med Univ, Sch Pharm, Dept Pharmacol, Nanning 530021, Guangxi, Peoples R China
[2] Guangxi Med Univ, Affiliated Canc Hosp, Dept Hepatobiliary Surg, Nanning 530021, Guangxi, Peoples R China
[3] Guangxi Med Univ, Affiliated Hosp 1, Dept Pathol, Nanning 530021, Guangxi, Peoples R China
[4] Columbia Univ Coll Phys & Surg, Dept Med, Lung Biol Lab, Div Pulm Allergy & Crit Care Med, New York, NY 10032 USA
[5] Guangxi Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanning 530021, Guangxi, Peoples R China
[6] Guangxi Med Univ, Ctr Translat Med, Nanning 530021, Guangxi, Peoples R China
关键词
MMP-8; TGF-beta; 1; Hepatocellular carcinoma; Metastasis; PI3K/Akt/Rac1; pathway; HUMAN BREAST-CANCER; EPITHELIAL-MESENCHYMAL TRANSITION; TGF-BETA; MATRIX METALLOPROTEINASES; CELL-LINES; POOR-PROGNOSIS; EXPRESSION; INVASION; METASTASIS; GROWTH;
D O I
10.1016/j.canlet.2016.02.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The efficiency of surgery in hepatocellular carcinoma (HCC) is limited due to metastasis and recurrence, but the molecular mechanisms are unclear. Here, we show that MMP-8 and TGF-beta 1 accumulate in highly invasive HCC cell lines and invasive HCC patient tissues. Upregulation of MMP-8 and TGF-beta 1 correlated with changes in cellular epithelial-mesenchymal transition (EMT) phenotypes and HCC migration and invasion. The expression of TGF-beta 1 was markedly restored by MMP-8 overexpression in TGF-beta 1-depleted HCC cells mainly via the activation of PI3K/Akt/Rac1 pathway. Similarly, the expression of MMP-8 was restored by TGF-beta 1 treatment in MMP-8-depleted HCC cells mainly through the activation of the same PI3K/Akt/Rac1 pathway. MMP-8 expression was significantly related to TGF-beta 1 expression in HCC patient tissues, and high expression of MMP-8 or TGF-beta 1 was significantly associated with TNM stage and HCC metastasis. Specifically, patients with high co-expression of MMP-8 and TGF-beta 1 had a shorter time-to-recurrence than those with low co-expression. Therefore, the reciprocal positive interplay between MMP-8 and TGF-beta 1 contributes to HCC invasion and metastasis by inducing EMT mainly through the PI3K/Akt/Rac1 pathway. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:85 / 95
页数:11
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