Elevated expression of syntenin in breast cancer is correlated with lymph node metastasis and poor patient survival

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.

Overexpression of syntenin enhances hepatoma cell proliferation and invasion: Potential roles in human hepatoma

“…egFR belongs to the erbB proto-oncogene receptors family (erbB tyrosine kinase receptors), and its cognate ligand has been considered as a common component of various cancer types to induce tumor growth (23,24). EGFR overexpression has been confirmed in multiple carcinomas including breast cancer, urothelial cell carcinoma and hepatoma (10,16). It is believed that egFR can trigger a cascade of multiple signaling pathways to regulate cancer cell proliferation, maintenance, invasion, metastasis, survival and prognosis (16,17,25,26).…”

“…As a PDZ domain-containing molecule, syntenin can exert multiple roles and regulate diverse and central physiologic processes (8,9). The function of syntenin in cancer has attracted increasing attention for its important roles in the development of various cancers, including melanoma, breast and bladder cancer (10,12,13). It has been confirmed that syntenin is highly expressed in several cancer cells and tissues, and it is involved in the progression of cancer, including cancer cell growth, invasion and metastasis (9,21,22).…”

“…Syntenin comprises four separate structural domains; the presence of two tandem PDZ domains (PDZ1 and PDZ2) is the notable feature, reflecting its indispensable role in assembling cell signaling processes. The function of syntenin has attracted increasing attention regarding its critical roles in cancer growth, invasion and metastasis (9)(10)(11). Extensive studies have demonstrated that syntenin is upregulated in several types of cancer, including breast cancer, melanoma and bladder cancer (10,12,13).…”

“…The function of syntenin has attracted increasing attention regarding its critical roles in cancer growth, invasion and metastasis (9)(10)(11). Extensive studies have demonstrated that syntenin is upregulated in several types of cancer, including breast cancer, melanoma and bladder cancer (10,12,13). Overexpression of syntenin in breast cancer cells promotes cell migration, invasion and tumor growth, as well as poor patient survival, indicating a significant role in breast cancer progression (10).…”

“…Extensive studies have demonstrated that syntenin is upregulated in several types of cancer, including breast cancer, melanoma and bladder cancer (10,12,13). Overexpression of syntenin in breast cancer cells promotes cell migration, invasion and tumor growth, as well as poor patient survival, indicating a significant role in breast cancer progression (10). Blocking syntenin expression inhibits melanoma cell migration, growth, invasion and metastasis by suppressing the p38 MAPK and NF-κB pathway (12).…”