Tousled-like kinase 1 promotes gastric cancer progression by regulating the tumor growth factor-beta signaling pathway  

作　　者：Ruo-Chuan Sun Jing Li Ya-Xian Li Hui-Zhen Wang Emre Dal Ming-Liang Wang Yong-Xiang Li 

机构地区：[1]Department of General Surgery,The First Affiliated Hospital of Anhui Medical University,Hefei 230022,Anhui Province,China [2]Department of Oncological Sciences,University of Utah,Salt Lake City,UT 84112,United States

出　　处：《World Journal of Gastroenterology》2023年第44期5919-5934,共16页世界胃肠病学杂志（英文版）

基　　金：Supported by the Key Programs of the Educational Commission of Anhui Province,No.2023AH053313;the Research Project of Higher Education in Anhui Province in 2022,No.2022AH051192.

摘　　要：BACKGROUND The role of Tousled-like kinase 1(TLK1)in in gastric cancer(GC)remains unclear.AIM To investigate the expression,biological function,and underlying mechanisms of TLK1 in GC.METHODS We measured TLK1 protein expression levels and localized TLK1 in GC cells and tissues by western blot and immunofluorescence,respectively.We transfected various GC cells with lentiviruses to create TLK1 overexpression and knockdown lines and established the functional roles of TLK1 through in vitro colony formation,5-ethynyl-2`-deoxyuridine,and Transwell assays as well as flow cytometry.We applied bioinformatics to elucidate the signaling pathways associated with TLK1.We performed in vivo validation of TLK1 functions by inducing subcutaneous xenograft tumors in nude mice.RESULTS TLK1 was significantly upregulated in GC cells and tissues compared to their normal counterparts and was localized mainly to the nucleus.TLK1 knockdown significantly decreased colony formation,proliferation,invasion,and migration but increased apoptosis in GC cells.TLK1 overexpression had the opposite effects.Bioinformatics revealed,and subsequent experiments verified,that the tumor growth factor-beta signaling pathway was implicated in TLK1-mediated GC progression.The in vivo assays confirmed that TLK1 promotes tumorigenesis in GC.CONCLUSION The findings of the present study indicated that TLK1 plays a crucial role in GC progression and is,therefore,promising as a therapeutic target against this disease.

关 键 词：Gastric cancer Tousled-like kinase 1 Tumor growth factor-beta Tumour progression Targeted therapy 

分 类 号：R735.2[医药卫生—肿瘤]