Xuechao Jia1,2, Chuntian Huang1,2, Yamei Hu1,2, Qiong Wu1,2, Fangfang Liu1,2, Wenna Nie2, Hanyong Chen3, Xiang Li1,2, Zigang Dong4,5,6, Kangdong Liu7,8,9,10,11. 1. Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China. 2. China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. 3. The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA. 4. Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China. dongzg@zzu.edu.cn. 5. China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. dongzg@zzu.edu.cn. 6. Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China. dongzg@zzu.edu.cn. 7. Department of Pathophysiology, The School of Basic Medical Sciences, AMS, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China. kdliu@zzu.edu.cn. 8. China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. kdliu@zzu.edu.cn. 9. Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, Henan, China. kdliu@zzu.edu.cn. 10. Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan, China. kdliu@zzu.edu.cn. 11. State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, Henan, China. kdliu@zzu.edu.cn.
Abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. METHODS: TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. RESULTS: TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. CONCLUSIONS: TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. METHODS:TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. RESULTS:TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. CONCLUSIONS:TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.
Authors: Takaomi Sanda; Jeffrey W Tyner; Alejandro Gutierrez; Vu N Ngo; Jason Glover; Bill H Chang; Arla Yost; Wenxue Ma; Angela G Fleischman; Wenjun Zhou; Yandan Yang; Maria Kleppe; Yebin Ahn; Jessica Tatarek; Michelle A Kelliher; Donna S Neuberg; Ross L Levine; Richard Moriggl; Mathias Müller; Nathanael S Gray; Catriona H M Jamieson; Andrew P Weng; Louis M Staudt; Brian J Druker; A Thomas Look Journal: Cancer Discov Date: 2013-03-07 Impact factor: 39.397
Authors: Ana Paula de Oliveira; Jackson Roberto Guedes da Silva Almeida; Ivanildo Viana Borges; Emanuella Chiara Valença Pereira; Thiala Alves Feitosa; Raira Feitosa Dos Santos; Raimundo Gonçalves de Oliveira-Junior; Larissa Araújo Rolim; Lucas Gustavo Ferreira Cordeiro Viana; Luciano Augusto de Araújo Ribeiro; Alan Diego da Conceição Santos; Pedro José Rolim-Neto Journal: PeerJ Date: 2019-01-15 Impact factor: 2.984