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
来源：
CANCER LETTERS | 2016年 / 374卷 / 01期
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
相关论文
共 53 条
  • [1] Expression of matrix metalloproteinase 8 (MMP-8) and tyrosinase-related protein-1 (TYRP-1) correlates with the absence of metastasis in an isogenic human breast cancer model
    Agarwal, D
    Goodison, S
    Nicholson, B
    Tarin, D
    Urquidi, V
    [J]. DIFFERENTIATION, 2003, 71 (02) : 114 - 125
  • [2] [Anonymous], CELL BIOL RES THER S
  • [3] [Anonymous], CELL RES
  • [4] [Anonymous], SCIENTIFICWORLDJOURN
  • [5] Loss of collagenase-2 confers increased skin tumor susceptibility to male mice
    Balbín, M
    Fueyo, A
    Tester, AM
    Pendás, AM
    Pitiot, AS
    Astudillo, A
    Overall, CM
    Shapiro, SD
    López-Otín, C
    [J]. NATURE GENETICS, 2003, 35 (03) : 252 - 257
  • [6] The Vav-Rac1 pathway in cytotoxic lymphocytes regulates the generation of cell-mediated killing
    Billadeau, DD
    Brumbaugh, KM
    Dick, CJ
    Schoon, RA
    Bustelo, XR
    Leibson, PJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (03) : 549 - 559
  • [7] TGF-β1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-κB/IL-6/MMP-2
    Binker, Marcelo G.
    Binker-Cosen, Andres A.
    Gaisano, Herbert Y.
    de Cosen, Rodica H.
    Cosen-Binker, Laura I.
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 405 (01) : 140 - 145
  • [8] Timeline - Matrix metalloproteinases: a tail of a frog that became a prince
    Brinckerhoff, CE
    Matrisian, LM
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (03) : 207 - 214
  • [9] MMP-2 alters VEGF expression via αVβ3 integrin-mediated PI3K/AKT signaling in A549 lung cancer cells
    Chetty, Chandramu
    Lakka, Sajani S.
    Bhoopathi, Praveen
    Rao, Jasti S.
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2010, 127 (05) : 1081 - 1095
  • [10] Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers
    Curran, S
    Dundas, SR
    Buxton, J
    Leeman, MF
    Ramsay, R
    Murray, GI
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (24) : 8229 - 8234
123456