A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma  

作　　者：Ya-Qing Zhou Xi-Xi Cheng Shuai He Shu-Qiang Liu Yi-Qi Li Pan-Pan Wei Chun-Ling Luo Jin-Xin Bei 

机构地区：[1]State Key Laboratory of Oncology in South China,Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy,Guangdong Provincial Clinical Research Center for Cancer,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center,Guangzhou 510060,P.R.China [2]P Department of Experimental Research,Sun Yat-sen University Cancer Center,Guangzhou 510060,P.R.China [3]Department of Medical Oncology,National Cancer Centre of Singapore,Singapore

出　　处：《Journal of Genetics and Genomics》2024年第10期997-1006,共10页遗传学报（英文版）

基　　金：This work was supported by the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061);the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141);National Natural Science Foundation(82261160657);Chang Jiang Scholars Program(J.-X.B.);Special Support Program of Guangdong(J.-X.B.)。

摘　　要：Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

关 键 词：PLD1 NF-κB pathway RELA Nasopharyngeal carcinoma(NPC) TUMORIGENESIS Positive feedback loop 

分 类 号：R739.63[医药卫生—肿瘤]