A controlled random gene perturbation method identifies ARPC1B gene as a key regulator of cancer metastasis

作     者：De Chang Hongzhen Du Xiaowei Chen Xiaocui Bian Wenjia Tian Jing Shen Yiju Wei Yunpeng Jiang Charles Dela Cruz Lixin Xie Lokesh Sharma Kailong Li De Chang;Hongzhen Du;Xiaowei Chen;Xiaocui Bian;Wenjia Tian;Jing Shen;Yiju Wei;Yunpeng Jiang;Charles Dela Cruz;Lixin Xie;Lokesh Sharma;Kailong Li

作者机构：College of Pulmonary and Critical Care MedicineChinese PLA General HospitalBeijing 100083China Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Section of Pulmonary and Critical Care and Sleep MedicineDepartment of MedicineYale University School of MedicineNew HavenCT 06520USA Department of Biochemistry and BiophysicsPeking University Health Science CenterBeijing 100191China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2023年第10卷第3期

页      面：687-689页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This study was supported by funding from The National Key Research and Development Program of China(No.2021YFC2302300) Beijing Nova Program Interdisciplinary Cooperation Project(DC No.Z191100001119021) Chinese PLA General Hospital Youth Project(DC No.QNF19074) Beijing Nova Program Project(DC No.Z171100001117012) China 13th Five-year National Key Grant(LXX,No.2018ZX09201013) the Fundamental Research Funds for the Central Universities(KL No.BMU2021YJ073). 

主　　题：metastasis cancer random 

摘      要：The discovery of clinically useful targets to treat specific pathological conditions can provide novel therapeutic approaches.To unbiasedly identify key genes related to tumor metastasis,we developed a random gene perturbation method using a piggyBac transposon system under the control of a doxycycline regulated promoter.Using this random gene perturbation method and utilizing a mouse model of metastatic pancreatic cancer,we identified genes dysregulated in metastasized cells from a random mutagenesis library after multiple rounds of in vivo selection.Analysis of these metastasized clones revealed the downregulation of ARPC1B gene.Our further mechanistic studies revealed that ARPC1B gene and its closely related gene ARPC1A worked in a regulatory loop to control tumor metastasis.These findings validate that piggyBac transposon mediated random gene perturbation is a powerful tool to investigate the functional relevance of novel genes and the ARPC1A/B axis is a potential key regulator of tumor metastasis.