Norepinephrine may promote the progression of Fusobacterium nucleatum related colorectal cancer via quorum sensing signalling

ABSTRACT

Fusobacterium nucleatum (F. nucleatum) is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of F. nucleatum 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 F. nucleatum related CRC (p < 0.01). In vitro studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of F. nucleatum. Moreover, chronic stress significantly increased the colon tumour burden of Apc^Min/+ mice infected with F. nucleatum (p < 0.01), which was decreased by a catecholamine inhibitor (p < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of F. nucleatum 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.

KEYWORDS:

• Stress
• norepinephrine
• Fusobacterium nucleatum
• colorectal cancer
• autoinducer-2

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics statement

This study was approved by the Institutional Review Board of the Affiliated Hospital of North Sichuan Medical College (Nanchong, China), and informed consent was obtained from all participants prior to enrolment (Approval ID: No. K2017027).

All animal experiments and protocols were approved by the Animal Care and Animal Experiment Ethics Committee of the North Sichuan Medical College (Approval ID: No. 201702004). Six-week-old male C57BL/6-Apc^Min/+ mice were purchased from Jiangsu JiCui Yaokang Biotechnology Co., Ltd. and raised in an SPF environment at the Animal Experiment Center of North Sichuan Medical College.

Consent for publication

The manuscript is approved by all the participants.

Author contributions

The work reported in this paper was performed by the authors unless clearly specified in the text. XHD, ZZT, and LY conducted the experiments and analysed the data. XHD, ZZT, LY and MZ drafted the manuscript. MZ and XSF refined and approved the final manuscript. XSF conceived and designed the study. Other co-authors performed helpful work. All authors have contributed to the manuscript and approved the submitted version.

Data Availability statement

The authors confirm that the data supporting the findings of this study are available in the article and its supplementary materials.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2350904.

Additional information

Funding

This work was supported by a National Natural Science Foundation of China [No. 81972315] grant to Xiangsheng Fu.