title: GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways.
abstract: Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4) has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer.
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China. jiancmu@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China. zhanghongyan516@163.com.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Structure-Based Drug Design &amp; Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. jianwang.chem@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China. 18640209060@163.com.
authors.forename: Liang-Hao
authors.initials: LH
authors.lastname: You
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China. zrzym111@126.com.
authors.forename: Rui-Zhi
authors.initials: RZ
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Structure-Based Drug Design &amp; Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. dongmeiz-67@163.com.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Structure-Based Drug Design &amp; Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. mscheng@263.net.
authors.forename: Mao-Sheng
authors.initials: MS
authors.lastname: Cheng
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China. fli@mail.cmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; C116367:PAK4 protein, human; D054462:p21-Activated Kinases
keywords: GL-1196; PAK4; gastric cancer; small molecular compound