• BMB Reports
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• 제39권2호
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• pp.132-139
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• 2006

Vascular endothelial cadherin (VE-cadherin), which belongs to the classical cadherin family, is localized at adherens junctions exclusively in vascular endothelial cells. Biochemical and biomechanical cues regulate the VE-cadherin adhesive potential by triggering the intracellular signals. VE-cadherin-mediated cell adhesion is required for cell survival and endothelial cell deadhesion is required for vascular development. It is therefore crucial to understand how VE-cadherin-based cell adhesion is controlled. This review summarizes the inter-endothelial cell adhesions and introduces our recent advance in Rap1-regulated VE-cadherin adhesion. A further analysis of the VE-cadherin recycling system will aid the understanding of cell adhesion/deadhesion mechanisms mediated by VE-cadherin in response to extracellular stimuli during development and angiogenesis.

• Childhood Kidney Diseases
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• 제17권2호
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• pp.79-85
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• 2013

목적: 단백뇨 질환의 실험모델인 puromycin aminonucleoside (PAN)에서 관찰할 수 있는 족세포의 병리학적 이상에 있어서 P-cadherin의 변화를 생체 외 족세포 배양실험을 통하여 알아보고자 하였다. 방법: PAN에 의한 족세포의 P-cadherin의 변화를 생체 외 배양실험을 통해 알아보고자 백서 사구체 상피세포(GEpC)를 배양하여 다양한 농도의 PAN을 투여하여 confocal 현미경을 통하여 P-cadherin의 분포를 관찰하였고, Western blotting 과 RT-PCR을 사용하여 P-cadherin 발현의 변화를 관찰하였다. 결과: 외곽세포질에 분포하는 P-cadherin은 단일세포 혹은 응집환경에서 PAN의 농도가 올라갈수록 내부로 응집되는 현상를 볼 수 있었다. Western 분석에서, P-cadherin 단백양은 PAN에 농도-의존적으로, 특히, 고농도인 50 mg/mL에서 24시간과 48시간이 노출 조건에서 각각 21.9% (P< 0.05)와 31.9% (P<0.01)의 의미 있는 감소소견을 보였다. RT-PCR에서도 48시간에서 50 mg/mL PAN을 첨가한 조건에서 23.5%의 의미 있는 감소를 보였다(P<0.05). 결론: PAN은 족세포에서 P-cadherin을 세포막으로부터 내부로의 응집을 유발하고, P-cadherin mRNA의 발현 감소와 단백수준에서 양의 감소를 초래함으로서, 단백뇨의 발생에 기여할 것이라 사료된다.

• 대한임상검사과학회지
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• 제55권1호
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• pp.37-44
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• 2023

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.

• 대한임상검사과학회지
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• 제51권3호
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• pp.360-369
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• 2019

Cadherin은 원형질막에 존재하며 세포-세포 결합에 관여하며, 황체 구조 유지에 필수적인 단백질이다. 본 연구에서는 prostaglandin F2 alpha ($PGF2{\alpha}$)가 황체의 협막세포(luteal theca cells, LTCs)의 E-cadherin, N-cadherin 및 세포-세포부착에 미치는 영향에 대해서 수행하였다. 황체세포는 소의 황체중기 조직으로부터 분리하였으며, 황체세포 중에서 mesenchymal 세포 형태학적 특성을 가지는 세포만을 분리하여 LTCs로 판단하였다. 이 후 steroidogenic 기능 및 혈관세포 유무를 판단하기 위해 $3{\beta}$-HSD 및 VEGF2R mRNA 발현을 확인하였으며, E-cadherin 및 N-cadherin mRNA를 사용하여 LTCs 내 cadherin의 존재여부를 판단하였다. 또한 0, $10^{-5}$, $10^{-4}$ 및 $10^{-3}M$ $PGF2{\alpha}$를 24시간 동안 처리하여 LTCs의 E- 및 N-cadherin 단백질을 관찰한 후 세포-세포 접착 실험을 실시하였다. 그 결과, LTCs에서 $3{\beta}$-HSD mRNA가 발현되었지만, VEGFR2 mRNA는 발현되지 않았으며, E-cadherin 및 N-cadherin mRNA 모두 발현되는 것을 확인하였다. 또한 E-및 N-cadherin 단백질은 $10^{-5}$, $10^{-4}$ 및 $10^{-3}M$ $PGF2{\alpha}$를 처리한 LTCs에서 응집되어 발현되는 것을 확인하였으며, $PGF2{\alpha}$에 의해 LTCs의 세포부착 효율이 유의적으로 감소된 것을 확인하였다. 결론적으로 $PGF2{\alpha}$는 LTCs의 E- 및 N-cadherin을 붕괴시켜 세포부착을 감소시켰고, 이러한 결과는 황체퇴행의 새로운 원인을 밝혀 내기 위한 cadherin과 세포부착의 역할을 이해하는데 중요한 자료로 활용될 것으로 판단된다.

• IMMUNE NETWORK
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• 제13권5호
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• pp.213-217
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• 2013

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5149-5153
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• 2012

Introduction: This study assessed the relationship of E-cadherin mRNA and protein expression with the diagnosis of lung cancer with the aim of providing an auxiliary diagnostic method. Methods: Semi-quantitative nested RT-PCR and western blotting were applied to detect E-cadherin mRNA transcripts and protein, respectively, in 30 cases of diagnostic lung cancer, 30 cases of clinically suspected patients with lung cancer and 30 cases of other disease. Immunohistochemical staining was also used to detect E-cadherin. Results: Remarkably decreased levels of relative E-cadherin mRNA value and increased E-cadherin protein negativity were observed in probable lung cancer, when compared with possible lung cancer and others. With a threshold of 1.45, relative E-cadherin mRNA value showed a sensitivity of 90% and a specifity of 83% for the diagnosis of lung cancer. The combination of decreased relative E-cadherin mRNA value and negative E-cadherin protein increased the specificity and sensitivity. Conclusion: These data suggest that Chinese patients with diagnostic lung cancer have similar decreased levels of relative E-cadherin mRNA and E-cadherin protein value in the lung cancer tissues as in lung cancer patients in other countries. Measurement of relative E-cadherin mRNA and protein values in lung cancer tissues has potential for lung cancer diagnosis.

• 생명과학회지
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• 제19권6호
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• pp.705-710
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• 2009

Sodium butyrate (NaBt)는 장에서 탄수화물대사로부터 생겨나는 짧은 천연지방산 사슬로 다양한 인간 암세포들 에게서 강력한 항암효능을 나타냄이 보고된 바 있지만 자세한 기전은 아직 알려져 있지 않다. 이 논문에서 우리는 NaBt가 주요 세포부착분자이면서 종양억제인자의 일종인 E-cadherin의 발현을 세포-특이적으로 촉진하는 기전을 연구하였다. 또한 NaBt는 E-eadherin의 발현을 촉진하는 것으로 알려진 p21의 발현도 증가시켰지만, NaBt에 의하여 증가한 p21은 E-cadherin의 활성화와 관련이 없음이 밝혀졌다. 그 대신에 NaBt는 CCAAT-box를 통한 E-cadherin 유전자의 프로모터 활성을 증가시킴으로써 E-cadherin의 발현을 전사수준에서 촉진하는 것 같다. 이렇게 NaBt에 의하여 증가된 E-cadherin은 주로 세포간 접촉면에 위치하면서 Hep3B 세포를 더 분화된 형태로 유도하여 NaBt의 항암활성이 나타나는 것 같다.

• 대한세포병리학회지
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• 제12권2호
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• pp.81-87
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• 2001

The differentiation between reactive mesothelial and carcinoma cells in serous effusion cytology can be a diagnostic challenge based on morphology alone. The expression of some cell adhesion molecules may be helpful in the differential diagnosis. This study evaluated the usefulness of E-cadherin Immunocytochemistry for discrimination of carcinoma cells from reactive mesothelial cells. Alcohol fixed, paraffin embedded cell blocks taken from 42 reactive and 102 malignant serous effusions with histologically confirmed diagnoses were immunostained with monoclonal antibody to E-cadherin by LSAB method. E-cadherin expression was identified in only 2 benign reactive serous effusions(5%) whereas 91 malignant serous effusions(89%) expressed E-cadherin The differences in immunostaining for E-cadherin between reactive and malignant serous effusions were statistically significant(p < 0.001). The sensitivity and specificity of the E-cadherin immunostaining for carcinoma cells were 89% and 95%, respectively. In conclusion, E-cadherin is a useful diagnostic adjunct for differentiation between reactive mesothelial and carcinoma cells in serous effusions.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2003-2007
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• 2012

Purpose: E-cadherin is a transmemberane protein which is responsible for adhesion of endothelial cells. The aim of our study was to assess existing evidence of associations between reduced expression of E-cadherin and prognosis of ovarian cancer with a discussion of potential approaches to exploiting any prognostic value for improved clinical management. Methods: We conducted a meta-analysis of 9 studies (n=915 patients) focusing on the correlation of reduced expression of E-cadherin with overall survival. Data were synthesized with random or fixed effect hazard ratios. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for E-cadherin positivity, and methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that reduced expression of E-cadherin positivity was associated with poor overall survival (OS), HR= 2.10, 95% CI:1.13-3.06. Conclusion: The overall survival of the E-cadherin negative group with ovarian cancer was significant poorer than the E-cadherin positive group. Upregulation of E-cadherin is an attractive therapeutic approach that could exert significant effects on clinical outcome of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5715-5719
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• 2012

The relation between cyclooxygenase enzymes and E-cadherin, along with the roles of these markers in the prediction of survival in optimally cytoreduced serous ovarian cancer patients was investigated. Individuals who underwent primary staging surgery and achieved optimal cytoreduction (largest residual tumor volume <1 cm) constituted the study population. Specimens of 32 cases were immunohistochemically examined for cyclooxygenase-1, cyclooxygenase-2, and E-cadherin. Two could not be evaluated for E-cadherin and cyclooxygenase-1. Overall, 14/30, 19/30, and 15/32 cases were positive for E-cadherin, cyclooxygenase-1, and cyclooxygenase-2, respectively. The expressions of E-cadherin and cyclooxygenase-2 were inversely correlated (p:0.02). E-cadherin expression was related with favorable survival (p<0.001). The relation between the expression of cyclooxygenase enzymes and poor survival did not reach statistical significance. On multivariate analysis, E-cadherin appeared as an independent prognostic factor for survival. In conclusion, E-cadherin expression is strongly linked with favorable survival. E-cadherin and cyclooxygenase 2 may interact with each other during the carcinogenesis-invasion process. Further studies clarifying the relation between E-cadherin and cyclooxygenase enzymes may lead to new preventive and therapeutic targets in ovarian cancer.