title: Inhibition of Mnk-eIF4E pathway sensitizes the efficacy to chemotherapy in anaplastic thyroid cancer.
abstract: OBJECTIVE
  We investigated whether MAPK-interacting kinase (Mnk) inhibition sensitizes anaplastic thyroid cancer (ATC) cellular response to chemotherapy.
  
  
  METHODS
  In vitro and in vivo methods were used to examine the combinatory effects of cisplatin with Mnk inhibition and its underlying mechanism.
  
  
  RESULTS
  Mnk inhibition by pharmacological or genetic approaches inhibits proliferation and induces apoptosis of ATC cells and enhances the effects of cisplatin in in vitro and in vivo. Mechanistically, cisplatin increases eIF4E phosphorylation in a dose- and time-dependent manner in ATC cells. Mnk inhibitors sensitize the efficacy of cisplatin by inhibiting cisplatin-induced eIF4E phosphorylation.
  
  
  CONCLUSIONS
  Targeting Mnk-eIF4E pathway provides a therapeutic strategy by sensitizing ATC response to chemotherapeutic drug.
authors: Thyroid Surgery Department, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors: Kun
authors: K
authors: Hu
authors: Endocrinology Department, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors: Juan
authors: J
authors: Zhang
authors: Galactophore Department, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors: Min
authors: M
authors: Yu
authors: School of Basic Medical Sciences, Hubei University of Science & Technology, Xianning, People's Republic of China.
authors: Chang'e
authors: C
authors: Xiong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D039561:Eukaryotic Initiation Factor-4E; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin
keywords: Mnk; chemotherapy; eIF4E; thyroid cancer