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

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

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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 cell proliferation 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-κB 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.

PLD1NF-κB pathwayRELANasopharyngeal carcinoma(NPC)TumorigenesisPositive feedback loop

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

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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

Department of Experimental Research,Sun Yat-sen University Cancer Center,Guangzhou 510060,P.R.China

Department of Medical Oncology,National Cancer Centre of Singapore,Singapore

Guangdong Basic and Applied Basic Research FoundationSci-Tech Project Foundation of Guangzhou CityNational Natural Science FoundationChang Jiang Scholars Program(J.-X.B.)Special Support Program of Guangdong(J.-X.B.).This study was supported by the Hong Kong Research Grant Council(RGC)Themebased ReSpecial Support Program of Guangdong(J.-X.B.).This study was supported by the Hong Kong Research Grant Council(RGC)Themebased Re

2024A15150130612023A04J214182261160657T12-703/22-RT12-703/23-N

2024

10.1016/j.jgg.2024.06.004

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(10)