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Abstract
IntroductionSyntenin is a scaffolding-PDZ domain-containing protein. Although it is reported that syntenin is associated with melanoma growth and metastasis, the possible role of syntenin in breast cancer has not been well elucidated. The present study investigated the expression and function of syntenin in breast cancer.MethodsReal-time polymerase chain reaction (PCR) and Western blots were used to determine the mRNA and protein expression of syntenin. With a combination of overexpression and RNA interference, the effect of syntenin on migration, invasion, and ERK1/2 activation was examined in breast cancer cell lines. The effect of syntenin in vivo was assessed with an orthotropic xenograft tumor model in BALB/c nu/nu mice. In addition, the expression level of syntenin in clinical breast cancer tissues was evaluated with immunohistochemistry. The Kaplan-Meier survival curve was used to evaluate patient survival, and the Cox proportional hazards model was used for multivariate analysis.ResultsOur study showed that syntenin expression was upregulated in high-metastasis breast cancer cell lines and breast cancer tissues. Overexpression of syntenin in breast cancer cells promoted cell migration and invasion in vitro. Moreover, overexpression of syntenin promoted breast tumor growth and lung metastasis in vivo. We further showed that activation of integrin β1 and ERK1/2 was required for syntenin-mediated migration and invasion of breast cancer cells. The correlation between syntenin expression and tumor size (P = 0.011), lymph node status (P = 0.001), and recurrence (P = 0.002) was statistically significant. More important, syntenin expression in primary tumors was significantly related to patients' overall survival (OS; P = 0.023) and disease-free survival (DFS; P = 0.001). Its status was an independent prognostic factor of OS (P = 0.049) and DFS (P = 0.002) in our cohort of patients.ConclusionsThese results suggest that syntenin plays a significant role in breast cancer progression, and it warrants further investigation as a candidate molecular marker of breast cancer metastasis and a potential therapeutic target.
Highlights
IntroductionIt is reported that syntenin is associated with melanoma growth and metastasis, the possible role of syntenin in breast cancer has not been well elucidated
The high-metastatic-potential cell line MDAMB-435 had higher expression of syntenin than did low-invasive cell lines. These findings suggest a potential correlation between syntenin expression and the metastatic ability of breast cancer cell lines
Our study shows that syntenin expression is upregulated in high-metastasis breast cancer cell lines and breast cancer tissues
Summary
It is reported that syntenin is associated with melanoma growth and metastasis, the possible role of syntenin in breast cancer has not been well elucidated. Syntenin is a scaffolding-PDZ domain-containing protein involved phosphatase-D, neurofaschin, neurexin, schwannomin ( known as merlin), IL-5 receptor, various glutamate receptor subtypes, the syndecan family of heparan sulfate proteoglycans, and ubiquitin [6,11], indirectly implicating its role in a variety of cellular processes. Inhibition of p38 or JNK MAPK did not have any effect on syntenin-induced invasion in HEK 293T cells [13]. This discrepancy might be explained by cell typespecific action of syntenin. The diversity of syntenininteraction partners suggests that syntenin may have flexible cell-type-specific roles
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