Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7
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...
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| Format: | Article |
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The Korean Society for Clinical Laboratory Science
2023-03-01
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| Series: | Korean Journal of Clinical Laboratory Science |
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| Online Access: | http://www.kjcls.org/journal/view.html?doi=10.15324/kjcls.2023.55.1.37 |
| _version_ | 1797854977892286464 |
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| author | Da-Hye KANG Sang-Hyeon YOO Ju-Eun HONG Ki-Jong RHEE |
| author_facet | Da-Hye KANG Sang-Hyeon YOO Ju-Eun HONG Ki-Jong RHEE |
| author_sort | Da-Hye KANG |
| collection | DOAJ |
| description | 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 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. Finally, we report 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. |
| first_indexed | 2024-04-09T20:15:01Z |
| format | Article |
| id | doaj.art-19b3d0bfbbcc48e1b429e1161ad6286d |
| institution | Directory Open Access Journal |
| issn | 1738-3544 |
| language | English |
| last_indexed | 2024-04-09T20:15:01Z |
| publishDate | 2023-03-01 |
| publisher | The Korean Society for Clinical Laboratory Science |
| record_format | Article |
| series | Korean Journal of Clinical Laboratory Science |
| spelling | doaj.art-19b3d0bfbbcc48e1b429e1161ad6286d2023-03-31T08:54:35ZengThe Korean Society for Clinical Laboratory ScienceKorean Journal of Clinical Laboratory Science1738-35442023-03-01551374410.15324/kjcls.2023.55.1.37kjcls.2023.55.1.37Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7Da-Hye KANG0Sang-Hyeon YOO1Ju-Eun HONG2Ki-Jong RHEE3Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus, Wonju, KoreaDepartment of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus, Wonju, KoreaDepartment of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus, Wonju, KoreaDepartment of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus, Wonju, KoreaEnterotoxigenic 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 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. Finally, we report 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.http://www.kjcls.org/journal/view.html?doi=10.15324/kjcls.2023.55.1.37enterotoxigenic bacteroides fragilise-cadherinproteasomestaurosporine |
| spellingShingle | Da-Hye KANG Sang-Hyeon YOO Ju-Eun HONG Ki-Jong RHEE Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7 Korean Journal of Clinical Laboratory Science enterotoxigenic bacteroides fragilis e-cadherin proteasome staurosporine |
| title | Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7 |
| title_full | Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7 |
| title_fullStr | Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7 |
| title_full_unstemmed | Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7 |
| title_short | Bacteroides fragilis Toxin Induces Cleavage and Proteasome Degradation of E-cadherin in Human Breast Cancer Cell Lines BT-474 and MCF7 |
| title_sort | bacteroides fragilis toxin induces cleavage and proteasome degradation of e cadherin in human breast cancer cell lines bt 474 and mcf7 |
| topic | enterotoxigenic bacteroides fragilis e-cadherin proteasome staurosporine |
| url | http://www.kjcls.org/journal/view.html?doi=10.15324/kjcls.2023.55.1.37 |
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