Global Microbiome Congress

Abstract

Although cancer is considered as a genetic disease, epigenetic dysregulation are intensively implicated in human cancers, especially nasopharyngeal carcinoma (NPC). As a newly active component, tumor-resident microbiota is present in various types of cancer, however its impact on cancer epigenetic program remains obscure. Here, through an integration of microbiome profiling, methylation sequencing, transcriptomics, clinical analysis, bacterial culture, and in vitro and in vivo experiments, we identified a representative strain Prevotella intermedia, which profoundly reshapes host metabolic signals and epigenetic changes to promote NPC metastasis. DnaK, as a secretory protein of P. intermedia, forms a complex with host glucose regulatory protein 78 (GRP78) to activate the protein kinase R-like endoplasmic reticulum kinase (PERK) /activating transcription factor 4 (ATF4) axis. ATF4 transcriptionally activates the key metabolic enzymes involved in serine, glycine, and one-carbon (SGOC) metabolism, leading to an increased generation of S-adenosylmethionine (SAM). Furthermore, we demonstrate a positive feedback loop in which SAM accumulation elevates H3K4Me3 levels and regulates chromatin accessibility to potentiate the ATF4 function, ultimately synergistically facilitating DNA hypermethylation. Our study reveals a novel epigenetic reprogramming mechanism of host cells modulated by the intratumoral microbiota and provides novel perspectives for future cancer therapy. 

Biography

Dr. Na Liu obtained her M.D. of Oncology at University of South China in 2007 and Ph.D. of Oncology at Sun Yat-sen University in 2013. She is currently a Prociple investigator (PI) in State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center. She has published more than 50 papers in reputed journals