Fusobacterium nucleatum promotes proliferation in oesophageal squamous cell carcinoma via AHR/CYP1A1 signalling.

ABSTRACT

Fusobacterium nucleatum (Fn) is reportedly involved in poor prognosis of oesophageal squamous cell carcinoma (ESCC), but the responsible mechanisms remain unclear. The present study aimed to explore the function of Fn in ESCC progression, and to identify the key genes or signals involved. Fluorescence in situ hybridization and quantitative PCR assays were applied to measure the abundance of Fn in ESCC tissues, finding that ESCC tissues displayed a higher abundance of Fn compared to adjacent tissues. Furthermore, Fn abundance in advanced ESCC tissues was found to be higher than that in early stage ESCC. The proliferation assays and wound healing assays indicated that Fn infection promoted ESCC cell proliferation and migration. Based on high-throughput sequencing, cytochrome P450 1A1 (CYP1A1) was the most significantly upregulated (eightfold increase) gene, and AKT signalling was activated in KYSE-450 cells treated with Fn. Knocking down CYP1A1 or inactivating AKT signalling with LY294002 downregulated p-AKTS473 , inhibited cell proliferation, and compromised the proliferation effect induced by Fn in both in vitro and in vivo experiments. Inactivating the aryl hydrocarbon receptor (AHR) by CH-223191 reversed CYP1A1 expression induced by Fn and inhibited the proliferation of ESCC cells. Taken together, our findings indicate that Fn may promote ESCC cell proliferation via AHR/CYP1A1/AKT signalling. Targeting Fn or AHR/CYP1A1 signalling could yield approaches relevant to the treatment of ESCC.