FCN2 inhibits epithelial-mesenchymal transition-induced metastasis of hepatocellular carcinoma via TGF-β/Smad signaling

被引:68
作者
Yang, Guangchao [1 ]
Liang, Yingjian [1 ]
Zheng, Tongsen [1 ]
Song, Ruipeng [1 ]
Wang, Jiabei [1 ]
Shi, Huawen [1 ]
Sun, Boshi [1 ]
Xie, Changming [1 ]
Li, Yuejin [1 ]
Han, Jihua [1 ]
Pan, Shangha [1 ]
Lan, Yaliang [1 ]
Liu, Xirui [1 ]
Zhu, Mingxi [1 ]
Wang, Yan [1 ]
Liu, Lianxin [1 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 1, Key Lab Hepatosplen Surg, Minist Educ,Dept Gen Surg, Harbin 150001, Heilongjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Hepatocellular carcinoma; FCN2; EMT; TGF-beta; BINDING LECTIN; L-FICOLIN; BETA; CANCER; GROWTH; POLYMORPHISMS; PROGRESSION; RESISTANCE;
D O I
10.1016/j.canlet.2016.05.007
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hepatocellular carcinoma (HCC) is currently still a major cause of cancer-related deaths. Identifying early metastatic biomarkers and therapeutic targets for HCC is of great importance. Emerging evidence suggest that epithelial-mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is crucial for improving HCC. In this study, we find Ficolin-2 (FCN2) plays an essential role in metastasis and EMT of HCC. FCN2 expression is downregulated in HCC cells and tissues. Low level of FCN2 in HCCs is correlated with aggressive metastatic features, and would be a prognostic factor for overall disease-free survival of HCC patients. Ectopic expression of FCN2 markedly inhibits HCC cells migration, invasion as well as EMT in vitro and in vivo. Moreover, TGF-beta is found contribute to the function of FCN2 in suppressing metastasis and EMT of HCC. Collectively, our data suggest that FCN2 may have prognostic value in HCC metastasis. Additionally, the FCN2/TGF-beta/EMT axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:80 / 86
页数:7
相关论文
共 30 条
  • [1] Role of L-ficolin/mannose-binding lectin-associated serine protease complexes in the opsonophagocytosis of type III group B streptococci
    Aoyagi, Y
    Adderson, EE
    Min, JG
    Matsushita, M
    Fujita, T
    Takahashi, S
    Okuwaki, Y
    Bohnsack, JF
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 174 (01) : 418 - 425
  • [2] Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer
    Arellano-Garcia, Martha E.
    Li, Roger
    Liu, Xiaojun
    Xie, Yongming
    Yan, Xiaofei
    Loo, Joseph A.
    Hu, Shen
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2010, 11 (09): : 3106 - 3121
  • [3] Cytoplasmic PML promotes TGF-β-associated epithelial-mesenchymal transition and invasion in prostate cancer
    Buczek, M. E.
    Miles, A. K.
    Green, W.
    Johnson, C.
    Boocock, D. J.
    Pockley, A. G.
    Rees, R. C.
    Hulman, G.
    van Schalkwyk, G.
    Parkinson, R.
    Hulman, J.
    Powe, D. G.
    Regad, T.
    [J]. ONCOGENE, 2016, 35 (26) : 3465 - 3475
  • [4] Hepatocellular carcinoma
    Forner, Alejandro
    Llovet, Josep M.
    Bruix, Jordi
    [J]. LANCET, 2012, 379 (9822) : 1245 - 1255
  • [5] Goggins M, 1998, CANCER RES, V58, P5329
  • [6] Grady WM, 1999, CANCER RES, V59, P320
  • [7] TRIM proteins and cancer
    Hatakeyama, Shigetsugu
    [J]. NATURE REVIEWS CANCER, 2011, 11 (11) : 792 - 804
  • [8] Regulation of EMT by TGFβ in cancer
    Heldin, Carl-Henrik
    Vanlandewijck, Michael
    Moustakas, Aristidis
    [J]. FEBS LETTERS, 2012, 586 (14): : 1959 - 1970
  • [9] Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2
    Hummelshoj, T
    Munthe-Fog, L
    Madsen, HO
    Fujita, T
    Matsushita, M
    Garred, P
    [J]. HUMAN MOLECULAR GENETICS, 2005, 14 (12) : 1651 - 1658
  • [10] TGF-β signaling and epithelial-mesenchymal transition in cancer progression
    Katsuno, Yoko
    Lamouille, Samy
    Derynck, Rik
    [J]. CURRENT OPINION IN ONCOLOGY, 2013, 25 (01) : 76 - 84