Li Nanlin, Wang Hui, Fan Jing, Tong Chao, Yang Jixin, Wei Hongliang, Yi Jun, Ling Rui
Department of Vascular and Endocrine Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Oncotarget. 2014 Jan 15;5(1):249-57. doi: 10.18632/oncotarget.1502.
An isoform of the 14-3-3 protein family, 14-3-3θ has been linked with tumor cell proliferation and apoptosis. However, the role of 14-3-3θ in the progression of breast cancer remains unknown. Here, we report that 14-3-3θ plays a critical role in breast cancer metastasis and prognosis. The expression of 14-3-3θ was markedly higher in breast cancer tissues compared to adjacent normal tissues. A hospital-based study cohort of 216 breast cancer patients was evaluated in this study. The level of 14-3-3θ expression was determined and correlated based upon tumor clinicopathological features, disease-free survival, and overall survival. We found that overexpression of 14-3-3θ was correlated with advanced TNM stage (P<0.05), lymph node metastasis (P<0.05), and ER negative status (P<0.05). Breast cancer patients with high 14-3-3θ expression had a shorter overall survival and a higher rate of recurrence than those with low 14-3-3θ expression. Additionally, knockdown of 14-3-3θ expression in breast cancer cells inhibited metastasis in vitro. Similarly, an in vivo assay showed that 14-3-3θ knockdown dramatically suppressed the growth of breast cancer xenografts and inhibited tumor cell metastasis in a lung metastasis model. Thus, this study provided the first evidence that 14-3-3θ is a novel tumor suppressor and may serve as a candidate prognostic biomarker and target for new therapies in metastatic breast cancer.
14-3-3θ是14-3-3蛋白家族的一种亚型，与肿瘤细胞增殖和凋亡有关。然而，14-3-3θ在乳腺癌进展中的作用尚不清楚。在此，我们报告14-3-3θ在乳腺癌转移和预后中起关键作用。与相邻正常组织相比，14-3-3θ在乳腺癌组织中的表达明显更高。本研究评估了一个基于医院的216例乳腺癌患者的研究队列。根据肿瘤临床病理特征、无病生存期和总生存期确定并关联14-3-3θ的表达水平。我们发现14-3-3θ的过表达与晚期TNM分期（P<0.05）、淋巴结转移（P<0.05）和ER阴性状态（P<0.05）相关。14-3-3θ高表达的乳腺癌患者总生存期较短，复发率高于14-3-3θ低表达的患者。此外，敲低乳腺癌细胞中14-3-3θ的表达可抑制体外转移。同样，体内试验表明，在肺转移模型中，敲低14-3-3θ可显著抑制乳腺癌异种移植物的生长并抑制肿瘤细胞转移。因此，本研究首次证明14-3-3θ是一种新型肿瘤抑制因子，可能作为转移性乳腺癌新疗法的候选预后生物标志物和靶点。
