FadA promotes DNA damage and progression of Fusobacterium nucleatum -induced colorectal cancer through up-regulation of
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(2020) 39:202
RESEARCH
Open Access
FadA promotes DNA damage and progression of Fusobacterium nucleatuminduced colorectal cancer through upregulation of chk2 Pin Guo1, Zibin Tian2, Xinjuan Kong2, Lin Yang2, Xinzhi Shan2, Bingzi Dong3, Xueli Ding2, Xue Jing2, Chen Jiang2, Na Jiang2 and Yanan Yu2*
Abstract Background: Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to nonmodifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods: C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results: Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of Ecadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions: In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to upregulation of chk2. Keywords: Colorectal cancer, Fusobacterium nucleatum, FadA, chk2, DNA damage, E-cadherin/β-catenin pathway
* Correspondence: [email protected] 2 Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao 266003, Shandong Province, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is
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