Abstract
BackgroundCD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined.MethodsThe contents of CD24 and epidermal growth factor receptor (EGFR) in gastric cancer cells (SGC-7901 and BGC-823) and non-malignant gastric epithelial cells (GES-1) were evaluated by Western blotting assay. Cellular EGFR staining was examined by immunofluorescence assay. Cell migration rate was measured by wound healing assay. The effects of depletion/overexperssion of CD24 on EGFR expression and activation of EGF/EGFR singaling pathways were evaluated by immunofluorescence, qPCR, Western blotting and flow cytometry techniques. RhoA activity was assessed by pulldown assay. CD24 and EGFR expression patterns in human gastric tumor samples were also investigated by immunohistochemistry staining.ResultsCD24 was overexpressed in human gastric cancer cells. Ectopic expression of CD24 in gastric epithelial cells augmented the expression of EGFR, while knockdown of CD24 in gastric cancer cells decreased the level of EGFR and cell migration velocity. To further explore the mechanisms, we investigated the effect of CD24 expression on EGF/EGFR signaling. We noticed that this effect of CD24 on EGFR expression was dependent on promoting EGFR internalization and degradation. Lower ERK and Akt phosphorylations in response to EGF stimulation were observed in CD24-depleted cells. In addition, we noticed that the effect of CD24 on EGFR stability was mediated by RhoA activity in SGC-7901 gastric cancer cells. Analysis of gastric cancer specimens revealed a positive correlation between CD24 and EGFR levels and an association between CD24 expression and worse prognosis.ConclusionThus, these findings suggest for the first time that CD24 regulates EGFR signaling by inhibiting EGFR internalization and degradation in a RhoA-dependent manner in gastric cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0787-y) contains supplementary material, which is available to authorized users.
Highlights
CD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined
We investigated the relevance of epidermal growth factor receptor (EGFR) expression in CD24 positive gastric cancer
CD24 is overexpressed and regulates EGFR expression in gastric cancer cells To assess the effect of CD24 on total EGFR level, we transfected human gastric cancer cells SGC-7901 with control small interfering RNA (siRNA) or siRNA for CD24
Summary
CD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined. CD24 is identified as a stem cell marker in intestinal and colonic epithelial cells [7, 8]. CD24 has been shown to be expressed in stem cell subpopulations from primary gastric, nasopharyngeal and colon tumors [9,10,11]. It is well known that negative expression of CD24 has been characterized as one of the biomarkers of breast cancer stem cells, resulting in functional promotion of breast tumor initiation and progression [12]. CD24 was observed to induce promoter activity and expression of the oncomir miR-21 via Src [18]. CD24 exerts its biological impacts based on multiple mechanisms, how CD24 contributes to gastric cancer progression remains largely unknown
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