Oncotarget
2014 Jul 30;5(14):5602-14.
doi: 10.18632/oncotarget.2136.
The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma
Junmou Hong 1, Zhenguo Liu 1, Hua Zhu 2, Xin Zhang 3, Yongju Liang 4, Shiyuan Yao 3, Fang Wang 4, Xiaoyun Xie 5, Bo Zhang 2, Tao Tan 2, Liwu Fu 4, Jing Nie 6, Chao Cheng 3
Affiliations expand
PMID: 24980814
PMCID: PMC4170621
DOI: 10.18632/oncotarget.2136
Abstract
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.
参考连接：
https://pubpeer.com/publications/28898202619A8B6A3A006237CFAF53
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