Lipopolysaccharide promotes metastasis via acceleration of glycolysis by the nuclear factor-κB/snail/hexokinase3 signaling axis in colorectal cancer

• DOI: 10.1186/s40170-021-00260-x
• Publication Date: 2021-05-12T18:03:00Z
• Authors: Xuesong Wu; Senmi Qian; Jun Zhang; Jieqiong Feng; Ke Luo; Lichao Sun; Liang Zhao; Yuliang Ran; Liang Sun; Jing Wang; Fangying Xu
• Keywords: 0301 basic medicine; 03 medical and health sciences; Snail; Caspase-1; Research; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Lipopolysaccharide; Hexokinase 3; NF-κB; RC254-282; Inflammasome; 3. Good health

Abstract Background Cancer cell is generally characterized by enhanced glycolysis. Inflammasome activation interaction with The concentration of lipopolysaccharide (LPS), a classic inflammasome activator, significantly higher in colorectal cancer tissue than normal intestinal mucosa. However, the mechanism LPS on glycolysis and metastasis has not been fully elucidated. This study aimed to investigate roles activation, glycolysis, metastasis, unravel metformin’s potential treatment CRC. Methods We detected motility following exposure CRC lines. Glycolysis analysis was performed, key glycolytic rate-limiting enzymes were detected. Dual-luciferase reporter gene assay, co-immunoprecipitation, chromatin immunoprecipitation (ChIP) analysis, ChIP-reChIP assay performed identify specific mechanisms Mouse models used determine effects metformin metastasis. Correlation expression various molecules 635 samples from Genome Atlas 83 our lab. Results activates caspase-1 through NF-κB upregulates Snail HK3 depending activation. potentiates migration invasion accelerated which could be reversed knockdown enzyme HK3. Nuclear upregulated under then forms complex NF-κB, directly binds promoter region upregulate Metformin suppresses NF-κB/Snail/HK3 signaling axis that activated inhibits LPS-induced In vivo, LPS-treated cells form more lungs mice, completely reverses this effect LPS. Conclusion inflammasomes promotes pathway prevent