KMID : 1101420230550010037
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Korean Journal of Clinical Laboratory Science 2023 Volume.55 No. 1 p.37 ~ p.44
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Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7
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Kang Da-Hye
Yoo Sang-Hyeon Hong Ju-Eun Rhee Ki-Jong
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Abstract
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Enterotoxigenic Bacteroides fragilis (ETBF) has been reported to promote colitis and colon cancer through the secretion of B. fragilis toxin (BFT), a zinc-dependent 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 ¥ã-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. Finally, we report that staurosporine also induces E-cadherin cleavage in the human breast cancer cell line, MCF7, through ¥ã-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.
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KEYWORD
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Enterotoxigenic Bacteroides fragilis, E-cadherin, Proteasome, Staurosporine
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