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Updated: Dec 22, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
SH3BGRL2 exerts a dual function in breast cancer growth and metastasis and is regulated by TGF-β1
Dou-Dou Li1,2,3, Ling Deng1, Shu-Yuan Hu1
1Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University Shanghai 200032, China.
Abstract:
SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2) is a poorly defined member of the SH3BGR gene family with potential roles in cell differentiation and tissue development. Here, we report for the first time that SH3BGRL2 exerts a dual function in breast tumor growth and metastasis. SH3BGRL2 was downregulated in a subset of primary breast tumors, and suppressed breast cancer cell proliferation and colony formation in vitro and xenograft tumor growth in vivo. Strikingly, SH3BGRL2 enhanced breast cancer cell migratory, invasive, and lung metastatic capacity. Mechanistic investigations revealed that SH3BGRL2 interacted with and transcriptionally repressed spectrin alpha, non-erythrocytic 1 (SPTAN1) and spectrin beta, non-erythrocytic 1 (SPTBN1), two important cytoskeletal proteins. Functional rescue assays further demonstrated that depletion of SH3BGRL2 reduced breast cancer cell invasive potential, which was partially rescued by knockdown of SPTAN1 and SPTBN1 using specific small interfering RNA. Moreover, transforming growth factor-β1 (TGF-β1) transcriptionally activated SH3BGRL2 expression in breast cancer cells through the canonical TGF-β receptor-Smad pathway. Collectively, these results establish a dual function of SH3BGRL2 in breast cancer growth and metastasis and uncover SH3BGRL2 as a downstream target of the TGF-β1 signaling pathway in breast cancer cells.
Insights
SH3BGRL2 protein suppresses breast cancer growth but promotes metastasis by repressing SPTAN1 and SPTBN1. Transforming growth factor-beta1 (TGF-β1) regulates SH3BGRL2 expression in breast cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- SH3BGRL2 is a poorly characterized protein with potential roles in development.
- Its function in cancer, particularly breast cancer, remains largely undefined.
Purpose of the Study:
- To investigate the role of SH3BGRL2 in breast tumor growth and metastasis.
- To elucidate the underlying molecular mechanisms and signaling pathways involved.
Main Methods:
- Analysis of SH3BGRL2 expression in primary breast tumors.
- In vitro cell proliferation, colony formation, migration, and invasion assays.
- In vivo xenograft tumor growth and metastasis studies.
- Interaction studies, transcriptional repression analysis, and functional rescue assays.
- Investigation of the TGF-β1 signaling pathway.
Main Results:
- SH3BGRL2 was downregulated in a subset of breast tumors.
- SH3BGRL2 suppressed breast cancer cell proliferation and tumor growth.
- SH3BGRL2 significantly enhanced breast cancer cell migration, invasion, and lung metastasis.
- SH3BGRL2 repressed the expression of cytoskeletal proteins SPTAN1 and SPTBN1.
- TGF-β1 transcriptionally activated SH3BGRL2 expression via the TGF-β receptor-Smad pathway.
Conclusions:
- SH3BGRL2 exhibits a dual role in breast cancer, inhibiting tumor growth while promoting metastasis.
- SH3BGRL2's metastatic potential is mediated through the repression of SPTAN1 and SPTBN1.
- SH3BGRL2 is a downstream target of TGF-β1 signaling in breast cancer.
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