Chronic restraint stress promotes the tumorigenic potential of oral squamous cell carcinoma cells by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/beta-catenin pathway

作者全名："Lou, Fangzhi; Long, Huiqing; Luo, Shihong; Liu, Yiyun; Pu, Juncai; Wang, Haiyang; Ji, Ping; Jin, Xin"

作者地址："[Lou, Fangzhi; Long, Huiqing; Luo, Shihong; Ji, Ping; Jin, Xin] Chongqing Med Univ, Key Lab Psychoseomadsy, Stomatol Hosp, Chongqing 401147, Peoples R China; [Lou, Fangzhi; Long, Huiqing; Luo, Shihong; Ji, Ping; Jin, Xin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China; [Liu, Yiyun; Pu, Juncai; Wang, Haiyang] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing 400042, Peoples R China; [Jin, Xin] Chongqing Med Univ, Stomatol Hosp, 426 Songshi North Rd, Chongqing 401147, Peoples R China"

通信作者："Jin, X (通讯作者)，Chongqing Med Univ, Stomatol Hosp, 426 Songshi North Rd, Chongqing 401147, Peoples R China."

来源：EXPERIMENTAL NEUROLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001001138800001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：359

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Chronic restraint stress; Oral squamous cell carcinoma; CXCL3; Lipid metabolism; Epithelial-mesenchymal transition

摘要："Chronic stress promotes tumor progression and may harm homeostasis of energy metabolism by disrupting key metabolic processes. Recently, emerging evidence that chemokines CXCL3 as a novel adipokine plays a new role in lipid metabolism and various human malignancies. However, the role and mechanism of the CXCL3 in oral squamous cell carcinoma (OSCC) progression and reprogramming lipid metabolism induced by chronic restraint stress is unclear. The analysis of transcriptome sequencing, LC-MS, GC-MS, CCK8, cell apoptosis assays, cell cycle analysis, qRT-PCR, ELISA, western blotting, immunofluorescence, immunohistochemistry, RNA interfer-ence and lentivirus transfection and a xenograft tumor growth and chronic restraint stress model were used to investigate the role of CXCL3 in the regulation of lipid metabolism and OSCC and explore the underlying mo-lecular mechanisms. We showed that CXCL3 plays a critical role in in fatty acid de novo synthesis and tumor growth induced by chronic restraint stress. We demonstrated that chronic restraint stress promoted lipid accu-mulation, OSCC growth and metastasis in a mouse xenograft model. CXCL3 knockdown and FH535, an inhibitor of Wnt/beta-catenin pathway, could attenuate fatty acid de novo synthesis, cell proliferation and epithelial-mesenchymal transition induced by chronic restraint stress in OSCC cells. Our findings demonstrate that chronic restraint stress promotes the proliferation and metastasis of OSCC by reprogramming fatty acid meta-bolism via CXCL3 mediated Wnt/beta-catenin pathway. Our study provides novel insights to help understand the underlying mechanisms of CXCL3 in OSCC progression induced by chronic restraint stress."

基金机构："National Natural ScienceFoundations of China [81870775, 81500855]; Natural Sci-ence Foundation of Chongqing [CSTB2022NSCQ-MSX1148]"

基金资助正文："Funding This work was supported by grants from the National Natural ScienceFoundations of China (No. 81870775, 81500855) and the Natural Sci-ence Foundation of Chongqing (No. CSTB2022NSCQ-MSX1148) ."