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Updated: Aug 7, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
A soluble truncated cadherin induces breast cancer cell apoptosis and growth inhibition
Xiao-Yu Shi1, He Lu, Wen-Lin Li
1INSERM, Institut Universitaire d'Hématologie, U553, Université Paris 7, 75010 Paris, France.
Purpose:
To identify the characteristics and function of the truncated cadherin cDNA which encodes a soluble molecule containing the sequence of VE-cadherin extracellular domain repeats from repeat 1 to 4 (designated as CED1-4) and a secreting signal peptide at N terminal.
Methods:
A pMSCV/CED1-4 vector was constructed. Recombinant retrovirus ReCED1-4 and ReEmpty were produced by 293 package cells and transfected into MDA-MB435 human breast cancer cells. The expression of CED1-4 in transfectants and their supernatant was analyzed by RT-PCR and Western blot, respectively. MDA-MB435 cell proliferation assays were performed in vitro and in vivo. CED-14-induced apoptosis was demonstrated using Annexin V binding, TUNEL and caspase 3 assays. The expression of integrin beta1 and c-fos mRNA was detected by RT-PCR.
Results:
The constructed soluble CED1-4 encoded 484 amino acids and a secreting signal peptide (27 amino acids). CED1-4 was expressed by MDA-MB435/CED1-4 cells, and detected in the supernatant of CED1-4 tranfectants. CED1-4 transfection significantly inhibited the growth of MDA-MB435 cells in vitro and in vivo. About 22-fold increase in the early apoptotic cells in MDA-MB435/CED1-4 cells was observed as compared with MDA-MB435/empty cells. Increased activity of caspase 3 in MDA-MB435/CED1-4 cells was more than two times as compared with that of the control cells. Interestingly, integrin beta1 transcriptional level in MDA-MB435/CED1-4 cells was down-regulated as compared with control cells. The resistance of fibronectin to CED1-4 apoptotic inducibility was confirmed by detection of caspase 3. The blockage of c-fos transcriptional expression was detected in MDA-MB435/CED1-4 cells.
Conclusions:
The soluble truncated cadherin may be considered an apoptotic inducer and growth inhibitor in the MDA-MB435 breast carcinoma cell line. Down-regulation of integrin beta1 and blockage of c-fos expression may be related to CED1-4-induced apoptosis and growth inhibition.
Insights
A soluble truncated cadherin (CED1-4) acts as an effective apoptotic inducer and growth inhibitor in breast cancer cells. This molecule down-regulates integrin beta1 and blocks c-fos expression, contributing to its anti-cancer effects.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Vascular Endothelial Cadherin (VE-cadherin) plays a crucial role in endothelial cell-cell adhesion.
- Truncated forms of cadherins may possess novel biological functions.
- Understanding the characteristics of soluble cadherin fragments is important for therapeutic development.
Purpose of the Study:
- To characterize a soluble truncated cadherin fragment (CED1-4) containing VE-cadherin extracellular domain repeats 1-4 and a signal peptide.
- To investigate the functional role of CED1-4 as a soluble molecule in breast cancer cells.
Main Methods:
- Construction of a pMSCV/CED1-4 retroviral vector.
- Transfection of MDA-MB435 human breast cancer cells with ReCED1-4 or ReEmpty retroviruses.
- Analysis of CED1-4 expression using RT-PCR and Western blot.
- In vitro and in vivo proliferation assays.
- Apoptosis assays (Annexin V, TUNEL, caspase 3).
- Detection of integrin beta1 and c-fos mRNA expression.
Main Results:
- Soluble CED1-4 (484 amino acids including a 27-amino acid signal peptide) was successfully expressed and secreted by MDA-MB435 cells.
- CED1-4 significantly inhibited MDA-MB435 cell proliferation both in vitro and in vivo.
- CED1-4 induced a significant increase in apoptosis, with a 22-fold rise in early apoptotic cells and a twofold increase in caspase 3 activity.
- Down-regulation of integrin beta1 and blockage of c-fos mRNA expression were observed in CED1-4 transfected cells.
Conclusions:
- Soluble truncated cadherin CED1-4 functions as an apoptotic inducer and growth inhibitor in the MDA-MB435 breast carcinoma cell line.
- The observed anti-cancer effects of CED1-4 are potentially mediated by the down-regulation of integrin beta1 and the blockage of c-fos expression.
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