Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-Cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7

¹ Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus, Wonju 26493, Korea

CBR 2024 , 5(1), 19–28; https://doi.org/10.18063/amcmr.v1i2.00120

© 2024 by the Author(s). Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )

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Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) has been reported to promote colitis and colon cancer through the secretion of B. fragilis toxin (BFT), a zincdependent metalloprotease. In colonic epithelial cells, BFT induces the cleavage of E-cadherin into the 80 kDa ectodomain and the 33 kDa membrane-bound intracellular domain. The resulting membrane-tethered fragment is then cleaved by γ-secretase forming the 28 kDa E-cadherin intracellular fragment. The 28 kDa cytoplasmic fragment is then degraded by an unknown mechanism. In this study, we found that the 28 kDa E-cadherin intracellular fragment was degraded by the proteasome complex. In addition, we found that this sequential E-cadherin cleavage mechanism is found not only in colonic epithelial cells but also in the human breast cancer cell line, BT-474. Lastly, we reported that staurosporine also induces E-cadherin cleavage in the human breast cancer cell line, MCF7, through γ-secretase. However, further degradation of the 28 kDa E-cadherin intracellular domain is not dependent on the proteasome complex. These results suggest that the BFT-induced E-cadherin cleavage mechanism is conserved in both colonic and breast cancer cells. This observation indicates that ETBF may
also play a role in the carcinogenesis of tissues other than the colon.

Keywords

Enterotoxigenic Bacteroides fragilis

E-cadherin

Proteasome

Staurosporine

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The authors declare no conflict of interest.

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