Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer.
Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer.
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脂多糖通过核因子-κB/snail/hexokinase3 信号轴加速糖酵解促进结肠直肠癌的转移。
DOI：
10.1186/s40170-021-00260-x
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发表时间：
2021-05-12
影响因子：
5.9
通讯作者：
Xu F
中科院分区：
文献类型：
--
作者：
Wu X;Qian S;Zhang J;Feng J;Luo K;Sun L;Zhao L;Ran Y;Sun L;Wang J;Xu F
癌细胞通常以糖酵解增强为特征。炎性小体活化与糖酵解相互作用。大肠癌组织中脂多糖（LPS）的浓度明显高于正常肠粘膜。然而，LPS对糖酵解和转移的作用机制尚未完全阐明。本研究旨在探讨脂多糖对大肠癌炎性小体活化、糖酵解和转移的作用，并揭示二甲双胍治疗大肠癌的潜力。我们在CRC细胞系中检测了LPS暴露后的炎性小体活化和细胞运动性。进行糖酵解分析，检测关键糖酵解限速酶。采用双荧光素酶报告基因分析、免疫共沉淀、染色质免疫沉淀（ChIP）分析和ChIP-reChIP分析等方法研究LPS对糖酵解的影响。使用小鼠转移模型来确定LPS和二甲双胍对转移的影响。在来自癌症基因组图谱的635个CRC样本和来自我们实验室的83个CRC样本中进行各种分子表达的相关性分析。LPS通过NF-κB激活caspase-1，并依赖caspase-1激活上调Snail和HK 3的表达。LPS依赖于加速的糖酵解增强迁移和侵袭，这可以通过敲低糖酵解限速酶HK 3来逆转。核Snail在LPS作用下被NF-κB上调，然后与NF-κB形成复合物，然后直接结合到HK 3启动子区以上调HK 3的表达。Metabolic抑制由LPS激活的NF-κB/Snail/HK 3信号传导轴，然后抑制LPS诱导的转移。在体内，LPS处理的细胞在小鼠肺中形成更多的转移，二甲双胍完全逆转了LPS的这种作用。LPS通过NF-κB激活癌细胞中的炎性体，并通过NF-κB/Snail/HK 3信号通路增强的糖酵解促进CRC中的转移。二甲双胍可阻断LPS的这种作用。在线版本包含补充材料，可通过10.1186/s40170-021-00260-x获得。
Cancer cell is generally characterized by enhanced glycolysis. Inflammasome activation is interaction with glycolysis. The concentration of lipopolysaccharide (LPS), a classic inflammasome activator, is significantly higher in colorectal cancer tissue than in normal intestinal mucosa. However, the mechanism of LPS on glycolysis and metastasis has not been fully elucidated. This study aimed to investigate the roles of LPS on inflammasome activation, glycolysis, and metastasis, and unravel metformin’s potential in treatment of CRC. We detected inflammasome activation and cell motility following LPS exposure in CRC cell lines. Glycolysis analysis was performed, and the key glycolytic rate-limiting enzymes were detected. Dual-luciferase reporter gene assay, co-immunoprecipitation, chromatin immunoprecipitation (ChIP) analysis, and ChIP-reChIP assay were performed to identify the specific mechanisms of LPS on glycolysis. Mouse metastasis models were used to determine the effects of LPS and metformin on metastasis. Correlation analysis of the expression of various molecules was performed in 635 CRC samples from The Cancer Genome Atlas and 83 CRC samples from our lab. LPS activates caspase-1 through NF-κB and upregulates the expression of Snail and HK3 depending on caspase-1 activation. LPS potentiates migration and invasion depending on accelerated glycolysis, which could be reversed by knockdown of glycolytic rate-limiting enzyme HK3. Nuclear Snail is upregulated by NF-κB under LPS treatment and then forms a complex with NF-κB, then directly binds to the HK3 promoter region to upregulate the expression of HK3. Metformin suppresses the NF-κB/Snail/HK3 signaling axis that is activated by LPS and then inhibits LPS-induced metastasis. In vivo, LPS-treated cells form more metastasis in the lungs of mice, and metformin completely reverses this effect of LPS. LPS activates inflammasomes in cancer cells through NF-κB and promotes metastasis through glycolysis enhanced by the NF-κB/Snail/HK3 signaling pathway in CRC. Metformin could prevent this effect of LPS. The online version contains supplementary material available at 10.1186/s40170-021-00260-x.
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影响因子：
5.2
作者：
Higurashi T;Nakajima A
通讯作者：
Nakajima A
DOI：
10.3322/caac.21398
发表时间：
2017-07-08
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Bhatt AP;Redinbo MR;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
4.6
作者：
Finucane, Orla M.;Sugrue, Jamie;Lynch, Marina A.
通讯作者：
Lynch, Marina A.
DOI：
10.1038/jid.2015.119
发表时间：
2015-08
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Lee DJ;Du F;Chen SW;Nakasaki M;Rana I;Shih VFS;Hoffmann A;Jamora C
通讯作者：
Jamora C
影响因子：
16.6
作者：
Martin-Montalvo, Alejandro;Mercken, Evi M.;Mitchell, Sarah J.;Palacios, Hector H.;Mote, Patricia L.;Scheibye-Knudsen, Morten;Gomes, Ana P.;Ward, Theresa M.;Minor, Robin K.;Blouin, Marie-Jose;Schwab, Matthias;Pollak, Michael;Zhang, Yongqing;Yu, Yinbing;Becker, Kevin G.;Bohr, Vilhelm A.;Ingram, Donald K.;Sinclair, David A.;Wolf, Norman S.;Spindler, Stephen R.;Bernier, Michel;de Cabo, Rafael
通讯作者：
de Cabo, Rafael