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Updated: Jun 6, 2026
10:37
Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
J C Martin1, B-S Herbert, B A Hocevar
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
British Journal of Cancer
|November 11, 2010
Summary
Loss of Disabled-2 (Dab2) expression in breast cancer cells promotes metastasis by activating epithelial-mesenchymal transition (EMT). This downregulation facilitates transforming growth factor beta (TGFβ) signaling, increasing tumor cell invasiveness.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Metastasis involves cancer cells acquiring migratory and invasive traits, similar to epithelial-mesenchymal transition (EMT).
- Disabled-2 (Dab2) is a potential tumor suppressor with reduced expression in cancers like breast cancer, but its role is not fully understood.
Purpose of the Study:
- To investigate the function of Disabled-2 (Dab2) in suppressing tumor initiation and progression.
- To determine the role of Dab2 in breast cancer metastasis.
Main Methods:
- Assessed Disabled-2 (Dab2) isoform expression in normal and breast tumor tissues using RT-PCR.
- Utilized shRNA to stably downregulate Dab2 in mammary epithelial cells and analyzed EMT markers via RT-PCR and western blot.
Main Results:
- Observed decreased expression of Dab2 isoforms (p96, p67) in breast tumors compared to normal tissue.
- Downregulation of Dab2 in normal mammary cells induced a constitutive EMT phenotype.
- Dab2 loss increased Ras/MAPK signaling, promoting an autocrine transforming growth factor beta (TGFβ) loop and TGFβ2 expression.
Conclusions:
- Loss of Dab2 expression in breast cancer may promote TGFβ-stimulated EMT.
- This process can increase the propensity for breast cancer metastasis.
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