The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma.
The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma.
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NUMB亚型1在食管鳞状细胞癌中的抑癌作用。
DOI：
10.18632/oncotarget.2136
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Cheng C
中科院分区：
文献类型：
--
作者：
Hong J;Liu Z;Zhu H;Zhang X;Liang Y;Yao S;Wang F;Xie X;Zhang B;Tan T;Fu L;Nie J;Cheng C
食管鳞状细胞癌（ESCC）是亚洲人群食管癌的主要组织学类型。迄今为止，很少有食管鳞癌的生物标志物被鉴定出来。在本研究中，我们发现了一种肿瘤抑制因子 NUMB 同种型 1 (NUMB-1)，作为 ESCC 患者有希望的预后生物标志物。与匹配的邻近非肿瘤组织相比，66.7% 的原发性 ESCC 组织中 NUMB-1 mRNA 下调。 NUMB-1 的低表达与肿瘤高复发率 (p=0.029) 和术后总生存率差 (p=0.016) 显着相关。为了进一步探讨 NUMB-1 调节 ESCC 的潜在机制，我们证明 NUMB-1 的异位表达通过诱导 G2/M 期停滞来抑制细胞增殖，同时伴随着 p21 和细胞周期蛋白 B1-cdc2 水平的增加。但对食管鳞癌细胞的凋亡没有影响。此外，NUMB-1的过表达可阻止上皮-间质转化，抑制ESCC细胞的侵袭和NOTCH通路，通过阻止Aurora-A在T288磷酸化而抑制Aurora-A活性，从而导致细胞周期停滞。总而言之，我们的研究结果表明 NUMB-1 具有肿瘤抑制剂的功能，并可作为 ESCC 患者的预后生物标志物；因此，NUMB-1可能是治疗ESCC的潜在新治疗靶点。
Esophageal quamous cell carcinoma (ESCC) is the predominant histological type of esophageal carcinoma in Asian populations. To date, few biomarkers have been identified for ESCC. In present study, we found a tumor suppressor, NUMB isoform 1 (NUMB-1), as a promising prognostic biomarker for patients with ESCC. NUMB-1 mRNA was downregulated in 66.7% of primary ESCC tissues when compared with matched adjacent non-tumor tissues. The low expression of NUMB-1 was significantly associated with high tumor recurrence (p=0.029) and poor post-operative overall survival (p=0.016). To further explore the underlying mechanisms by which NUMB-1 regulates ESCC, we demonstrated that ectopic expression of NUMB-1 inhibited cell proliferation through inducing G2/M phase arrest, which was accompanied by an increase in p21 and cyclin B1-cdc2 levels. However, it had no impact on apoptosis of ESCC cells. In addition, overexpression of NUMB-1 prevented epithelial-mesenchymal transition, inhibited invasion of ESCC cells and NOTCH pathway, suppressed Aurora-A activity by preventing phosphorylation of Aurora-A at T288 which resulted in cell cycle arrest. Taken together, our findings suggested NUMB-1 functions as a tumor-suppressor and serves as a prognositc biomarker for ESCC patients; thus, NUMB-1 may be a potential novel therapeutic target for treatment of ESCC.
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