Norepinephrine may promote the progression of <i>Fusobacterium nucleatum</i> related colorectal cancer via quorum sensing signalling

Abstract

<i>Fusobacterium nucleatum (F. nucleatum)</i> is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of <i>F. nucleatum</i> in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of <i>F. nucleatum</i> related CRC (<i>p</i> < 0.01). <i>In vitro</i> studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of <i>F. nucleatum</i>. Moreover, chronic stress significantly increased the colon tumour burden of Apc^Min/+ mice infected with <i>F. nucleatum</i> (<i>p</i> < 0.01), which was decreased by a catecholamine inhibitor (<i>p</i> < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of <i>F. nucleatum</i> related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.