Premium
Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β‐catenin modulator Annexin A1
Author(s) -
Rubinstein Mara Roxana,
Baik Jung Eun,
Lagana Stephen M,
Han Richard P,
Raab William J,
Sahoo Debashis,
Dalerba Piero,
Wang Timothy C,
Han Yiping W
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201847638
Subject(s) - fusobacterium nucleatum , wnt signaling pathway , dkk1 , colorectal cancer , cancer research , catenin , annexin , biology , cancer , chemistry , microbiology and biotechnology , porphyromonas gingivalis , signal transduction , apoptosis , bacteria , biochemistry , genetics
Fusobacterium nucleatum , a Gram‐negative oral anaerobe, is a significant contributor to colorectal cancer. Using an in vitro cancer progression model, we discover that F. nucleatum stimulates the growth of colorectal cancer cells without affecting the pre‐cancerous adenoma cells. Annexin A1, a previously unrecognized modulator of Wnt/β‐catenin signaling, is a key component through which F. nucleatum exerts its stimulatory effect. Annexin A1 is specifically expressed in proliferating colorectal cancer cells and involved in activation of Cyclin D1. Its expression level in colon cancer is a predictor of poor prognosis independent of cancer stage, grade, age, and sex. The FadA adhesin from F. nucleatum up‐regulates Annexin A1 expression through E‐cadherin. A positive feedback loop between FadA and Annexin A1 is identified in the cancerous cells, absent in the non‐cancerous cells. We therefore propose a “two‐hit” model in colorectal carcinogenesis, with somatic mutation(s) serving as the first hit, and F. nucleatum as the second hit exacerbating cancer progression after benign cells become cancerous. This model extends the “adenoma‐carcinoma” model and identifies microbes such as F. nucleatum as cancer “facilitators”.