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

Abstract

SummaryCD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n 5 80, r 5 0.425, P \ 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P \ 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P \ 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPARc, which mediates EGFR expression, although whether PPARc mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P \ 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer.2012 IUBMB IUBMB Life, 64(11): 911-920, 2012

Adenosine Stimulate Proliferation and Migration in Triple Negative Breast Cancer Cells

“…Consistent with this idea, it has been reported that CD73 is overexpressed in different types of tumors and cell lines. Interestingly, in breast cancer cells, CD73 overexpression has been associated with invasiveness and drug resistance [32],[33],[34]. …”

The Roles of CD73 in Cancer

“…More interestingly, downregulation of EGFR by siRNA resulted in inhibition of migration and invasion activities in pcDNA-NT5E transfected T-47D cells. In another study, researchers found that CD73 expression correlated positively to EGFR expression in MB-MDA-231 cells, and EGFR expression could be decreased by suppressing CD73 expression with siRNA [38]. These observations suggested that CD73 promoted tumor cell migration and invasion via regulating EGFR expression.…”

“…Thus, the promotive effect of CD73 on cancer cells proliferation in vitro may via other molecule which independent with adenosine, such as EGFR, which is a key molecule involved in cell growth. Recently, Zhi et al have found the regulative effect of CD73 on EGFR expression and phosphorylation in human breast cancer [38]. …”

Evaluation of tissue 5´-Nucleotidase as tumor marker in breast and brain tumors using receiver operating characteristic curve

“…Supernat et al showed that elevated CD73 expression in breast cancer can predict a good prognosis of the disease [26]. In addition, Zhi et al suggested that CD73 may be used as a potential prognostic & therapeutic biomarker for breast cancer [27].…”