In silico identification of oncogenic potential of fyn-related kinase in hepatocellular carcinoma

被引:111
作者
Chen, Jia-Shing [1 ]
Hung, Wei-Shiang [1 ]
Chan, Hsiang-Han [1 ]
Tsai, Shaw-Jenq [2 ,3 ]
Sun, H. Sunny [1 ,3 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Inst Mol Med, Tainan 70101, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Dept Physiol, Tainan 70101, Taiwan
[3] Natl Cheng Kung Univ, Ctr Biotechnol & Biosci, Bioinformat Ctr, Tainan 70101, Taiwan
关键词
RAK TYROSINE KINASE; TUMOR-SUPPRESSOR; BREAST-CANCER; LIVER-CANCER; GENE; ACTIVATION; PROLIFERATION; CELLS; RETINOBLASTOMA; METASTASIS;
D O I
10.1093/bioinformatics/bts715
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Results: By exploiting the information of conserved protein domains from the TAG, we identified 183 potential new TAGs. As a proof-of-concept, one predicted oncogene, fyn-related kinase (FRK), which shows an aberrant digital expression pattern in liver cancer cells, was selected for further investigation. Using 68 paired hepatocellular carcinoma samples, we found that FRK was up-regulated in 52% of cases (P < 0.001). Tumorigenic assays performed in Hep3B and HepG2 cell lines revealed a significant correlation between the level of FRK expression and invasiveness, suggesting that FRK is a positive regulator of invasiveness in liver cancer cells. Conclusion: These findings implied that FRK is a multitalented signal transduction molecule that produces diverse biological responses in different cell types in various microenvironments. In addition, our data demonstrated the accuracy of computational prediction and suggested that other predicted TAGs can be potential targets for future cancer research.
引用
收藏
页码:420 / 427
页数:8
相关论文
共 43 条
  • [1] GTK, a Src-related tyrosine kinase, induces nerve growth factor-independent neurite outgrowth in PC12 cells through activation of the Rap1 pathway -: Relationship to Shb tyrosine phosphorylation and elevated levels of focal adhesion kinase
    Annerén, C
    Reedquist, KA
    Bos, JL
    Welsh, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) : 29153 - 29161
  • [2] The FRK/RAK-SHB signaling cascade:: A versatile signal-transduction pathway that regulates cell survival, differentiation and proliferation
    Annerén, C
    Lindholm, CK
    Kriz, V
    Welsh, M
    [J]. CURRENT MOLECULAR MEDICINE, 2003, 3 (04) : 313 - 324
  • [3] Activation of Rap1 Promotes Prostate Cancer Metastasis
    Bailey, Candice L.
    Kelly, Patrick
    Casey, Patrick J.
    [J]. CANCER RESEARCH, 2009, 69 (12) : 4962 - 4968
  • [4] Oncogenic kinase signalling
    Blume-Jensen, P
    Hunter, T
    [J]. NATURE, 2001, 411 (6835) : 355 - 365
  • [5] Primary liver cancer:: Worldwide incidence and trends
    Bosch, FX
    Ribes, J
    Díaz, M
    Cléries, R
    [J]. GASTROENTEROLOGY, 2004, 127 (05) : S5 - S16
  • [6] BOWDEN GT, 1994, CANCER RES, V54, pS1882
  • [7] The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology
    Caldwell, Stephen
    Park, Sang H.
    [J]. JOURNAL OF GASTROENTEROLOGY, 2009, 44 : 96 - 101
  • [8] CANCE WG, 1994, CELL GROWTH DIFFER, V5, P1347
  • [9] Carrillo-Infante C, 2007, INT J ONCOL, V30, P1521
  • [10] Molecular mechanisms in hepatocellular carcinoma development
    Cha, C
    DeMatteo, RR
    [J]. BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY, 2005, 19 (01) : 25 - 37