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.

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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