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Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Xiuling Zhi1, Yingjian Wang, Jerry Yu

  • 1Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

IUBMB Life
|October 23, 2012
PubMed

Insights

CD73, an enzyme overexpressed in breast cancer, correlates with epidermal growth factor receptor (EGFR) expression. Targeting CD73 may offer a new therapeutic strategy for breast cancer, particularly in estrogen receptor-negative cases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • CD73 is an ecto-enzyme overexpressed in breast cancer cells.
  • Anti-CD73 therapies have shown potential in slowing breast cancer growth and metastasis.

Purpose of the Study:

  • To investigate the relationship between CD73 and epidermal growth factor receptor (EGFR) expression in breast cancer.
  • To explore the underlying mechanisms of CD73-mediated EGFR regulation.
  • To assess the prognostic significance of CD73 in breast cancer patients.

Main Methods:

  • Analysis of CD73 and EGFR expression in tissue arrays (n=80) and breast cancer cell lines.
  • Inhibition of CD73 using small shRNA and pharmacological inhibitors.
  • Reversal studies using adenosine and an adenosine A2 receptor agonist (NECA).
  • Investigation of CD73's role in EGFR phosphorylation via Src kinase.
  • Transcription factor (TF) assays to identify regulatory pathways (e.g., PPARγ).
  • Kaplan-Meier survival analysis using the KMplotter database.

Main Results:

  • A positive correlation was observed between CD73 and EGFR expression in vivo and in vitro.
  • Suppression of CD73 led to decreased EGFR expression, an effect reversed by adenosine agonists.
  • CD73 was found to regulate EGFR phosphorylation through Src kinase.
  • CD73 activity influences transcription factors like PPARγ, potentially mediating EGFR expression.
  • High CD73 expression was associated with significantly different recurrence-free survival in estrogen receptor-negative breast cancer.

Conclusions:

  • CD73 plays a significant role in regulating EGFR expression and phosphorylation in breast cancer.
  • Adenosine signaling is implicated in the CD73-EGFR pathway.
  • CD73 may serve as a prognostic biomarker, particularly in conjunction with EGFR coexpression in estrogen receptor-negative breast cancer.
  • Targeting CD73 presents a potential therapeutic avenue for breast cancer treatment.

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