Related Experiment Video
Updated: Jun 12, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Tetraspanin CD151 regulates transforming growth factor beta signaling: implication in tumor metastasis
Rafal Sadej1, Hanna Romanska, Dean Kavanagh
1Department of Pathology, School of Cancer Sciences, The University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Abstract:
Tetraspanin CD151 is associated with laminin-binding integrins and controls tumor cell migration and invasion. By analyzing responses of breast cancer cells to various growth factors, we showed that depletion of CD151 specifically attenuates transforming growth factor beta1 (TGFbeta1)-induced scattering and proliferation of breast cancer cells in three-dimensional Matrigel. CD151-dependent cell scattering requires its association with either alpha3beta1 or alpha6 integrins, but it is independent of the recruitment of CD151 to tetraspanin-enriched microdomains. We also found that CD151 regulates the compartmentalization of TGF-beta type I receptor (TbetaRI/ALK-5) and specifically controls the TGFbeta1-induced activation of p38. In contrast, signaling leading to activation of Smad2/3, c-Akt, and Erk1/2 proteins was comparable in CD151(+) and CD151(-) cells. Attenuation of TGFbeta1-induced responses correlated with reduced retention in the lung vascular bed, inhibition of pneumocyte-induced scattering of breast cancer cells in three-dimensional Matrigel, and decrease in experimental metastasis to the lungs. These results identify CD151 as a positive regulator of TGFbeta1-initiated signaling and highlight the important role played by this tetraspanin in TGFbeta1-induced breast cancer metastasis.
Insights
Tetraspanin CD151 regulates transforming growth factor beta1 (TGFβ1) signaling, controlling breast cancer cell scattering and proliferation. Its depletion inhibits TGFβ1-induced metastasis, highlighting its role in tumor cell invasion.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Tetraspanin CD151 is implicated in tumor cell migration and invasion.
- CD151 associates with laminin-binding integrins, influencing cellular processes.
Purpose of the Study:
- To investigate the role of CD151 in transforming growth factor beta1 (TGFβ1)-induced breast cancer cell behavior.
- To elucidate the specific signaling pathways regulated by CD151 in response to TGFβ1.
Main Methods:
- Analysis of breast cancer cell responses to TGFβ1 with and without CD151.
- Assessment of integrin associations and receptor compartmentalization.
- Evaluation of downstream signaling pathway activation (p38, Smad2/3, c-Akt, Erk1/2).
- In vivo metastasis assays in a mouse model.
Main Results:
- CD151 depletion specifically attenuated TGFβ1-induced scattering and proliferation of breast cancer cells in 3D Matrigel.
- CD151-dependent scattering required association with α3β1 or α6 integrins.
- CD151 regulated TGF-β type I receptor (TβRI/ALK-5) compartmentalization and specifically controlled TGFβ1-induced p38 activation.
- Signaling pathways Smad2/3, c-Akt, and Erk1/2 activation were comparable in CD151-positive and -negative cells.
- Reduced CD151 levels correlated with decreased lung metastasis.
Conclusions:
- CD151 acts as a positive regulator of TGFβ1-initiated signaling in breast cancer.
- CD151 plays a critical role in TGFβ1-induced breast cancer cell metastasis to the lungs.
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