MERTK as a novel therapeutic target in head and neck cancer

被引:19
|
作者
von Maessenhausen, Anne [1 ,2 ,3 ]
Sanders, Christine [1 ,2 ,3 ]
Thewes, Britta [1 ,2 ,3 ]
Deng, Mario [4 ,5 ,6 ,7 ]
Queisser, Angela [1 ,2 ,3 ]
Vogel, Wenzel [4 ,5 ,6 ,7 ]
Kristiansen, Glen [2 ,3 ]
Duensing, Stefan [8 ]
Schroeck, Andreas [3 ,9 ]
Bootz, Friedrich [3 ,9 ]
Brossart, Peter [3 ,10 ]
Kirfel, Jutta [2 ,3 ]
Heasley, Lynn [11 ]
Braegelmann, Johannes [1 ,3 ,10 ]
Perner, Sven [4 ,5 ,6 ,7 ]
机构
[1] Univ Hosp Bonn, Sect Prostate Canc Res, Bonn, Germany
[2] Univ Hosp Bonn, Inst Pathol, Bonn, Germany
[3] Univ Hosp Bonn, Ctr Integrated Oncol Cologne Bonn, Bonn, Germany
[4] Univ Hosp Luebeck, Pathol, Lubeck, Germany
[5] Leibniz Res Ctr Borstel, Lubeck, Germany
[6] Univ Hosp Luebeck, Pathol, Borstel, Germany
[7] Leibniz Res Ctr Borstel, Borstel, Germany
[8] Heidelberg Univ, Dept Urol, Heidelberg, Germany
[9] Univ Hosp Bonn, Dept Otorhinolaryngol Head & Neck Surg, Bonn, Germany
[10] Univ Hosp Bonn, Dept Hematol Oncol, Bonn, Germany
[11] Univ Colorado, Dept Craniofacial Biol, Anschutz Med Campus, Aurora, CO USA
关键词
head and neck cancer; MERTK; targeted therapy; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; COPY NUMBER; INHIBITION; EXPRESSION; MODELS; OVEREXPRESSION; AMPLIFICATION; RADIOTHERAPY;
D O I
10.18632/oncotarget.8724
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although head and neck cancer (HNSCC) is the sixth most common tumor entity worldwide therapy options remain limited leading to 5-year survival rates of only 50 %. MERTK is a promising therapeutic target in several tumor entities, however, its role in HNSCC has not been described yet. The aim of our study was to investigate the biological significance of MERTK and to evaluate its potential as a novel therapeutic target in this dismal tumor entity. In two large HNSCC cohorts (n=537 and n=520) we found that MERTK is overexpressed in one third of patients. In-vitro, MERTK overexpression led to increased proliferation, migration and invasion whereas MERTK inhibition with the small molecule inhibitor UNC1062 or MERTK knockdown reduced cell motility via the small GTPase RhoA. Taken together, we are the first to show that MERTK is frequently overexpressed in HNSCC and plays an important role in tumor cell motility. It might therefore be a potential target for selected patients suffering from this dismal tumor entity.
引用
收藏
页码:32678 / 32694
页数:17
相关论文
共 50 条
  • [41] Improving the therapeutic ratio in head and neck cancer
    Prestwich, Robin
    Dyker, Karen
    Sen, Mehmet
    LANCET ONCOLOGY, 2010, 11 (06): : 512 - 513
  • [42] The changing therapeutic landscape of head and neck cancer
    Cramer, John D.
    Burtness, Barbara
    Quynh Thu Le
    Ferris, Robert L.
    NATURE REVIEWS CLINICAL ONCOLOGY, 2019, 16 (11) : 669 - 683
  • [43] Novel therapeutics for head and neck cancer
    Kim, ES
    Kies, M
    Herbst, RS
    CURRENT OPINION IN ONCOLOGY, 2002, 14 (03) : 334 - 342
  • [44] Cyclooxygenase-2: A novel molecular target for the prevention and treatment of head and neck cancer
    Lin, DT
    Subbaramaiah, K
    Shah, JP
    Dannenberg, AJ
    Boyle, JO
    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2002, 24 (08): : 792 - 799
  • [45] NSP 5a3a: A Potential Novel Cancer Target in Head and Neck Carcinoma
    D'agostino, Luca
    Giordano, Antonio
    ONCOTARGET, 2010, 1 (06) : 423 - 435
  • [46] BAP1 Is a Novel Target in HPV-Negative Head and Neck Cancer
    Liu, Xiyou
    Kumar, Manish
    Yang, Liangpeng
    Molkentine, David P.
    Valdecanas, David
    Yu, Shiying
    Meyn, Raymond E.
    Heymach, John V.
    Skinner, Heath D.
    CLINICAL CANCER RESEARCH, 2018, 24 (03) : 600 - 607
  • [47] MERTK receptor tyrosine kinase is a therapeutic target in melanoma
    Schlegel, Jennifer
    Sambade, Maria J.
    Sather, Susan
    Moschos, Stergios J.
    Tan, Aik-Choon
    Winges, Amanda
    DeRyckere, Deborah
    Carson, Craig C.
    Trenthath, Dimitri G.
    Tentler, John J.
    Eckhardt, S. Gail
    Kuan, Pei-Fen
    Hamilton, Ronald L.
    Duncan, Lyn M.
    Miller, C. Ryan
    Nikolaishvili-Feinberg, Nana
    Midkiff, Bentley R.
    Liu, Jing
    Zhang, Weihe
    Yang, Chao
    Wang, Xiaodong
    Frye, Stephen V.
    Earp, H. Shelton
    Shields, Janie M.
    Graham, Douglas K.
    JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (05): : 2257 - 2267
  • [48] Neoadjuvant cisplatin for head and neck cancer: Simulation of a novel schedule for improved therapeutic ratio
    Marcu, Loredana G.
    Bezak, Eva
    JOURNAL OF THEORETICAL BIOLOGY, 2012, 297 : 41 - 47
  • [49] Inhibitor of DNA binding 2 is a novel therapeutic target for stemness of head and neck squamous cell carcinoma
    Bae, Woo Jin
    Koo, Bon Seok
    Lee, Sang Hyuk
    Kim, Jin Man
    Rho, Young Soo
    Lim, Jae Yol
    Moon, Jung Hwa
    Cho, Jae Hoon
    Lim, Young Chang
    BRITISH JOURNAL OF CANCER, 2017, 117 (12) : 1810 - 1818
  • [50] Novel therapeutic target for head and neck squamous cell carcinoma: HGF-MET signaling pathway
    Lau, Patrick Chi-pan
    Chan, Anthony Tak-cheung
    ANTI-CANCER DRUGS, 2011, 22 (07) : 665 - 673