Protein tyrosine phosphatase receptor-type δ acts as a negative regulator suppressing breast cancer

Xiaotang Yu1, Fan Zhang2, Jun Mao1

  • 1Department of Pathology and Forensic Medicine, Dalian Medical University, Dalian 116044, PR China.

Oncotarget
|December 13, 2017
PubMed

Insights

Restoring Protein tyrosine phosphatase receptor-type δ (PTPRD) may combat breast cancer. PTPRD loss enhances cancer stem cells, migration, and metastasis by activating STAT3 signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Protein tyrosine phosphatase receptor-type δ (PTPRD) is frequently inactivated in human cancers.
  • Dysregulation of PTPRD is implicated in cancer progression.

Purpose of the Study:

  • To investigate the role of PTPRD in regulating breast cancer stemness, epithelial-mesenchymal transition (EMT), and metastasis.
  • To elucidate the molecular mechanisms underlying PTPRD's function in breast cancer.

Main Methods:

  • PTPRD silencing using siRNA in breast cancer cells.
  • Assessment of stem cell properties (mammosphere, holoclone formation, CD44+/CD24- population, stem cell markers ALDH1, OCT4).
  • Evaluation of migration, invasion, EMT, and STAT3 signaling pathway activation.
  • Analysis of PTPRD expression in breast cancer stem cells (BCSCs) and its regulation by IL-6.

Main Results:

  • PTPRD silencing enhanced stem cell-like properties, promoted tumorigenicity, increased BCSCs, and upregulated stem cell markers.
  • PTPRD knockdown promoted cell migration, invasion, EMT, and STAT3 activation.
  • BCSCs exhibited low PTPRD levels and mesenchymal phenotypes.
  • IL-6 upregulated PTPRD, creating a negative feedback loop that dephosphorylated STAT3.

Conclusions:

  • PTPRD plays a crucial role in suppressing breast cancer stemness, EMT, and metastasis.
  • Restoring PTPRD expression may represent a therapeutic strategy to control breast cancer progression and metastasis by inhibiting the IL-6/STAT3 pathway.

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