Suppression of Aurora-A-FLJ10540 signaling axis prohibits the malignant state of head and neck cancer

被引:16
作者
Chen, Chang-Han [1 ,2 ,3 ,4 ,9 ,10 ]
Chang, Alice Y. W. [5 ]
Li, Shau-Hsuan [6 ]
Tsai, Hsin-Ting [1 ,2 ,3 ,4 ]
Shiu, Li-Yen [7 ]
Su, Li-Jen [8 ]
Wang, Wen-Lung [2 ,3 ,4 ,11 ]
Chiu, Tai-Jen [4 ,6 ]
Luo, Sheng-Dean [2 ,3 ,4 ]
Huang, Tai-Lin [4 ,6 ]
Chien, Chih-Yen [1 ,2 ,3 ,4 ]
机构
[1] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung, Taiwan
[2] Kaohsiung Chang Gung Mem Hosp, Dept Otolaryngol, Kaohsiung, Taiwan
[3] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan
[4] Kaohsiung Chang Gung Mem Hosp, Kaohsiung Chang Gung Head & Neck Oncol Grp, Kaohsiung, Taiwan
[5] Natl Cheng Kung Univ, Inst Physiol, Tainan 70101, Taiwan
[6] Chang Gung Univ, Coll Med, Dept Hematol Oncol, Kaohsiung, Taiwan
[7] I Shou Univ, E Da Hosp, Cell Therapy & Res Ctr, Dept Med Res, Kaohsiung, Taiwan
[8] Natl Cent Univ, Grad Inst Syst Biol & Bioinformat, Jhongli, Taiwan
[9] Natl Chi Nan Univ, Dept Appl Chem, Taoyuan, Taiwan
[10] Natl Chi Nan Univ, Grad Inst Biomed & Biomed Technol, Taoyuan, Taiwan
[11] Kaohsiung Chang Gung Mem Hosp, Dept Med Res, Kaohsiung, Taiwan
来源
MOLECULAR CANCER | 2015年 / 14卷
关键词
HNC; Aurora-A; FLJ10540; MMP-7 and MMP-10; SQUAMOUS-CELL CARCINOMA; AURORA-A; MATRIX METALLOPROTEINASE-2; TUMOR PROGRESSION; INHIBITOR MLN8237; POOR-PROGNOSIS; KINASE; OVEREXPRESSION; EXPRESSION; PROLIFERATION;
D O I
10.1186/s12943-015-0348-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Head and neck cancer (HNC) is a highly invasive cancer. Aurora-A has been reported for a number of malignancies. However, the identity of downstream effectors responsible for its aggressive phenotype in HNC remains underinvestigated. Methods: The mRNA and protein expression levels of Aurora-A and FLJ10540 were assessed in HNC specimens and cell lines using RT-qPCR, western blot, Oncomine, and microarray database analysis. The downstream molecular mechanisms of Aurora-A were confirmed by RT-qPCR, western blot, luciferase reporter, confocal microscopy analyses, immunoprecipitation, colony formation, cell viability, and xenograft model. Cellular functions in response to Aurora-A-modulated downstream targets such as FLJ10540 and MMPs were examined in vitro and in vivo, including cell growth, motility and chemosensitivity. Aurora-A/FLJ10540/MMPs expression was determined in cancer and adjacent normal tissues from HNC patients by immunohistochemistry approach. Results: In the current study, Aurora-A exhibited similar gene expression profiles with FLJ10540 by using accessibly public microarray and Oncomine database analysis, raising the possibility that these molecules might coordinately participate in cancer progression and metastasis of HNC. These two molecules connection were also examined in cell lines and tissues of HNC. Aurora-A overexpression could not only bind to the promoter of FLJ10540 to induce FLJ10540 expression, but also increase both mRNA and protein levels of MMP-7 and MMP-10 in HNC cells. Conversely, depletion of Aurora-A expression by using siRNA or Aurora-A kinase inhibitor, MLN8237, suppressed FLJ10540, MMP-7 and MMP-10 mRNA and protein expressions in vitro and in vivo. In addition, the FLJ10540-PI3K complex was destroyed by inhibition the Aurora-A kinase activity. Forced overexpression of FLJ10540 in Aurora-A-depleted or in MLN8237-treated HNC cells attenuated the effect on cytotoxicity to cisplatin. Elevated Aurora-A expression in HNC cells led to the characteristics of more aggressive malignancy, including enhanced chemoresistance and increased the abilities of proliferation, migration and invasion, which was required for FLJ10540/MMP-7 or FLJ10540/MMP-10 expressions. Finally, immunohistochemical analysis of human HNC specimens showed a significant positively correlation among Aurora-A, FLJ10540, MMP-7 and MMP-10 expressions. Conclusion: Together, our findings define a novel mechanism by which Aurora-A promotes cell malignancy, with potential implications for understanding the clinical action of Aurora-A.
引用
收藏
页数:18
相关论文
共 38 条
  • [21] Aurora A kinase (AURKA) in normal and pathological cell division
    Nikonova, Anna S.
    Astsaturov, Igor
    Serebriiskii, Ilya G.
    Dunbrack, Roland L., Jr.
    Golemis, Erica A.
    [J]. CELLULAR AND MOLECULAR LIFE SCIENCES, 2013, 70 (04) : 661 - 687
  • [22] Biological, diagnostic and therapeutic relevance of the MET receptor signaling in head and neck cancer
    Nisa, Lluis
    Aebersold, Daniel Matthias
    Giger, Roland
    Zimmer, Yitzhak
    Medova, Michaela
    [J]. PHARMACOLOGY & THERAPEUTICS, 2014, 143 (03) : 337 - 349
  • [23] Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma
    Reiter, Rudolf
    Gais, Peter
    Juetting, Uta
    Steuer-Vogt, Miriam K.
    Pickhard, Anja
    Bink, Karin
    Rauser, Sandra
    Lassmann, Silke
    Hoefler, Heinz
    Werner, Martin
    Walch, Axel
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (17) : 5136 - 5141
  • [24] Targeting Aurora kinase-A downregulates cell proliferation and angiogenesis in neuroblastoma
    Romain, Carmelle
    Paul, Pritha
    Kim, Kwang Woon
    Lee, Sora
    Qiao, Jingbo
    Chung, Dai H.
    [J]. JOURNAL OF PEDIATRIC SURGERY, 2014, 49 (01) : 159 - 165
  • [25] Recent advances in head and neck squamous cell carcinoma - A review
    Safdari, Yaghoub
    Khalili, Masoumeh
    Farajnia, Safar
    Asgharzadeh, Mohammad
    Yazdani, Yaghoub
    Sadeghi, Mahnaz
    [J]. CLINICAL BIOCHEMISTRY, 2014, 47 (13-14) : 1195 - 1202
  • [26] SCHLEGEL J, 1995, CANCER RES, V55, P6002
  • [27] The Aurora Kinase A Inhibitor MLN8237 Enhances Cisplatin-Induced Cell Death in Esophageal Adenocarcinoma Cells
    Sehdev, Vikas
    Peng, DunFa
    Soutto, Mohammed
    Washington, M. Kay
    Revetta, Frank
    Ecsedy, Jeffrey
    Zaika, Alexander
    Rau, Tilman T.
    Schneider-Stock, Regine
    Belkhiri, Abbes
    El-Rifai, Wael
    [J]. MOLECULAR CANCER THERAPEUTICS, 2012, 11 (03) : 763 - 774
  • [28] Expression Profiles and Clinical Correlations of Degradome Components in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma
    Stokes, Angela
    Joutsa, Juho
    Ala-aho, Risto
    Pitchers, Mark
    Pennington, Caroline J.
    Martin, Craig
    Premachandra, Don J.
    Okada, Yasunori
    Peltonen, Juha
    Grenman, Reidar
    James, Helen A.
    Edwards, Dylan R.
    Kahari, Veli-Matti
    [J]. CLINICAL CANCER RESEARCH, 2010, 16 (07) : 2022 - 2035
  • [29] Aurora-A controls cancer cell radio- and chemoresistance via ATM/Chk2-mediated DNA repair networks
    Sun, Huizhen
    Wang, Yan
    Wang, Ziliang
    Meng, Jiao
    Qi, Zihao
    Yang, Gong
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2014, 1843 (05): : 934 - 944
  • [30] Essential Roles of mTOR/Akt Pathway in Aurora-A Cell Transformation
    Taga, Makoto
    Hirooka, Eiji
    Ouchi, Toru
    [J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2009, 5 (05): : 444 - 450