Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β-catenin modulator Annexin A1
© 2019 The Authors..
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".
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
EMBO reports - 20(2019), 4 vom: 04. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rubinstein, Mara Roxana [VerfasserIn] |
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| Links: |
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| Themen: |
Annexin A1 |
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| Anmerkungen: |
Date Completed 30.04.2020 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/embr.201847638 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM294575219 |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a © 2019 The Authors. | ||
| 520 | |a 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" | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Fusobacterium nucleatum | |
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| 700 | 1 | |a Baik, Jung Eun |e verfasserin |4 aut | |
| 700 | 1 | |a Lagana, Stephen M |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Richard P |e verfasserin |4 aut | |
| 700 | 1 | |a Raab, William J |e verfasserin |4 aut | |
| 700 | 1 | |a Sahoo, Debashis |e verfasserin |4 aut | |
| 700 | 1 | |a Dalerba, Piero |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Timothy C |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Yiping W |e verfasserin |4 aut | |
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