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DACH1 suppresses breast cancer as a negative regulator of CD44

Hanxiao Xu1, Shengnan Yu1, Xun Yuan1

  • 1Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Scientific Reports
|June 30, 2017
PubMed

Insights

Dachshund homolog 1 (DACH1) suppresses breast cancer progression by inhibiting cancer stem cells and epithelial-mesenchymal transition. Higher DACH1 levels correlate with better patient survival, suggesting DACH1 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Dachshund homolog 1 (DACH1) is a cell fate factor implicated in tumorigenesis.
  • The precise anti-tumor mechanisms of DACH1 in breast carcinoma remain unclear.
  • Understanding DACH1's role is crucial for developing novel breast cancer therapies.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the anti-tumor effects of DACH1 in breast cancer.
  • To investigate the relationship between DACH1 expression and key cancer progression markers.
  • To evaluate DACH1 as a prognostic biomarker in breast carcinoma.

Main Methods:

  • Immunohistochemistry (IHC) staining of human breast tissues and mouse xenografts.
  • Analysis of public microarray and Gene Expression Omnibus (GEO) databases.
  • Correlation analysis with cancer stem cell (CSC) markers, epithelial-mesenchymal transition (EMT) inducers, and CD44 expression.

Main Results:

  • DACH1 expression is inversely correlated with high-grade, basal-like breast cancer and CSC/EMT markers.
  • Upregulation of DACH1 in Met-1 cells reduced tumorigenesis potential in mice.
  • Higher DACH1 expression in patients predicted prolonged survival and reduced recurrence/metastasis.
  • Cluster of differentiation 44 (CD44) showed an inverse correlation with DACH1 and predicted poor prognosis.

Conclusions:

  • DACH1 exhibits significant anti-tumor roles in breast carcinoma by suppressing CSCs and EMT.
  • DACH1 expression is a favorable prognostic biomarker for breast cancer patients.
  • CD44 may represent a novel therapeutic target regulated by DACH1 in breast cancer.

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