a Department of Thoracic Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
b Department of Pathology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
Cancer Biol Ther. 2018 Jan 2;19(1):34-41. doi: 10.1080/15384047.2016.1276131. Epub 2017 Dec 18.
Numb is a protein whose asymmetric segregation during cell division determines cell fate and has numerous functions relevant to multiple fields of study, including developmental neurobiology and cancer biology. Little is known about the role of Numb in esophageal squamous cell carcinoma (ESCC), the predominant histological esophageal carcinoma in Asian populations. In this study, we focused on the expression and biologic functions of Numb in the context of ESCC. From analysis of tissue microarrays with 212 patients, it was found that Numb was significantly upregulated in ESCC tissues compared with corresponding non-cancerous tissues. Kaplan-Meier survival analysis suggests that higher expression of Numb was significantly associated with a high tumor recurrence (p = 0.015) and poor overall post-surgical survival (p = 0.016). Using multiple Cox regression, the expression of Numb was determined to be an independent predictor of poor prognosis. When siRNA was used to knockdown Numb in ESCC cell lines, there was a consistent increase in caspase-3 dependent apoptosis and inhibition of cellular proliferation, as well as downregulation of expression of the cancer stem cell markers Oct-4, SOX-2 and Nanog. In addition, downregulated Numb expression was not significantly associated with the migration of ESCC cells. These results indicate that Numb acts as an oncoprotein and has potential as a novel prognostic biomarker and therapeutic target in ESCC patients.
Numb 是一种蛋白质，其在细胞分裂过程中的不对称分配决定了细胞命运，并具有与多个研究领域相关的多种功能，包括发育神经生物学和癌症生物学。关于 Numb 在食管鳞状细胞癌（ESCC）中的作用知之甚少，ESCC 是亚洲人群中主要的组织学食管癌。在这项研究中，我们专注于 Numb 在 ESCC 背景下的表达和生物学功能。通过对 212 例患者的组织微阵列进行分析，发现 Numb 在 ESCC 组织中明显上调，与相应的非癌组织相比。Kaplan-Meier 生存分析表明，Numb 的高表达与肿瘤复发率高（p = 0.015）和术后总生存率差（p = 0.016）显著相关。通过多 Cox 回归分析，确定 Numb 的表达是预后不良的独立预测因子。当使用 siRNA 敲低 ESCC 细胞系中的 Numb 时，细胞凋亡的 caspase-3 依赖性和细胞增殖的抑制一致增加，并且癌症干细胞标记物 Oct-4、SOX-2 和 Nanog 的表达下调。此外，下调的 Numb 表达与 ESCC 细胞的迁移没有显著相关性。这些结果表明，Numb 作为一种癌蛋白发挥作用，并有潜力成为 ESCC 患者的新型预后生物标志物和治疗靶点。
