title: PI3K/AKT-mediated upregulation of WDR5 promotes colorectal cancer metastasis by directly targeting ZNF407.
abstract: Colorectal cancer (CRC) is the third most common cause of cancer deaths, and has a high rate of liver and lung metastasis. Unfortunately, distant metastasis is the main barrier for advanced CRC therapy and leads to a very low survival rate. In this study, we identified WDR5, a vital factor that regulates vertebrate development and cell self-renewal and reprogramming, as a novel prognostic marker and therapeutic target for CRC patients. We demonstrate that WDR5 is upregulated in CRC tissues and promotes CRC metastasis both in vitro and in vivo. In an effort to investigate the impact of WDR5 on CRC cell fate, we treated CRC cells with growth factor and inhibitor. We report that WDR5 is a novel factor in the metastasis of CRC by triggering epithelial-mesenchymal transition (EMT) process in response to the PI3K/AKT signaling pathway. Moreover, WDR5 shows a direct binding to the ZNF407 promoter on regulating cellular EMT process, leading to CRC metastasis. Hence, our findings strongly position WDR5 as a valuable marker for CRC, and inhibiting WDR5 or the associated signaling pathways may be an effective strategy for the future development of anti-CRC therapy.
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Jiangxue
authors.initials: J
authors.lastname: Wu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Medical Oncology, Sichuan Cancer Hospital and Institute, Second People's Hospital of Sichuan Province, Chengdu 614000, PR China.
authors.forename: Changchuan
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430079, PR China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Ying
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Ranyi
authors.initials: R
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou 510060, PR China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, PR China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D045325:HCT116 Cells; D057809:HEK293 Cells; D019073:HT29 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009362:Neoplasm Metastasis / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C502547:WDR5 protein, human; C580839:ZNF407 protein, human