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

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

doi:10.1016/j.jgg.2024.06.004

Volume 51 Issue 10

Oct. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(10): 997-1006

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

doi: 10.1016/j.jgg.2024.06.004

a. 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;
b. Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China;
c. Department of Medical Oncology, National Cancer Centre of Singapore, Singapore

Funds:

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.), and Special Support Program of Guangdong (J.-X.B.). This study was supported by the Hong Kong Research Grant Council (RGC) Theme-based Research Scheme Funds (T12-703/22-R and T12-703/23-N).

Received Date: 2024-04-17
Accepted Date: 2024-06-06
Rev Recd Date: 2024-06-04

Available Online: 2025-06-06

Publish Date: 2024-06-15

Abstract

Abstract

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 overexpression 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.
- PLD1,
- NF-κB pathway,
- RELA,
- Nasopharyngeal carcinoma (NPC),
- Tumorigenesis,
- Positive feedback loop

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References(35)

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