Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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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

인간 유방암 세포주 BT-474와 MCF7에서 Bacteroides fragilis Toxin에 의한 E-cadherin 분절과 프로테아좀에 의한 분해

  • Da-Hye KANG (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus) ;
  • Sang-Hyeon YOO (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus) ;
  • Ju-Eun HONG (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus) ;
  • Ki-Jong RHEE (Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE campus)
  • 강다혜 (연세대학교 소프트웨어디지털헬스케어융합대학 임상병리학과) ;
  • 유상현 (연세대학교 소프트웨어디지털헬스케어융합대학 임상병리학과) ;
  • 홍주은 (연세대학교 소프트웨어디지털헬스케어융합대학 임상병리학과) ;
  • 이기종 (연세대학교 소프트웨어디지털헬스케어융합대학 임상병리학과)
  • Received : 2022.12.23
  • Accepted : 2022.12.29
  • Published : 2023.03.31
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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 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.

Enterotoxigenic Bacteroides fragilis (ETBF)는 염증성장 질환과 대장암을 유발하며 아연 의존성 metalloprotease인 B. fragilis toxin (BFT)를 분비한다. BFT는 epithelial cell의 E-cadherin을 80 kDa ectodomain과 33 kDa intracellular domain으로 분절을 유도한다. 생성된 E-cadherin intracellular domain은 순차적으로 γ-secretase에 의해 분절되어 28 kDa E-cadherin intracellular fragment은 아직까지 밝혀지지 않는 기작으로 분해된다. 본 연구에서는 BFT 유도 E-cadherin 분절로 인해 생성된 28 kDa E-cadherin intracellular fragment는 proteasome에 의해서 분해된다는 것을 확인하였다. 또한 BFT 유도 E-cadherin 분절 기작이 대장암 세포가 아닌 인간 유방암 세포주 BT-474 세포에서도 동일한 기작으로 일어남을 확인하였다. 마지막으로 staurosporine은 인간 유방암 세포주 MCF7 세포에서 E-cadherin의 분절을 유도하고 γ-secretase에 의한 E-cadherin intracellular domain의 분절이 일어났으나 proteasome에 의한 분해는 일어나지 않았다. 이러한 결과는 ETBF가 서식하는 대장이 아닌 유방에서도 BFT에 의한 E-cadherin 분절이 일어날 수 있으며 ETBF가 대장암 이외의 다른 암에도 관여할 수 있음을 시사한다.

Keywords

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