Oncotarget

Research Papers:

The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma

Junmou Hong, Zhenguo Liu, Hua zhu, Xin Zhang, Yongju Liang, Shiyuan Yao, Fang Wang, Xiaoyun xie, Bo Zhang, Tao Tan, Liwu Fu, Jing Nie and Chao Cheng _

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Oncotarget. 2014; 5:5602-5614. https://doi.org/10.18632/oncotarget.2136

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Abstract

Junmou Hong1,*, Zhenguo Liu1,*, Hua Zhu2, Xin Zhang1, Yongju Liang3, Shiyuan Yao1, Fang Wang3, Xiaoyun Xie4, Bo Zhang2, Tao Tan2, Liwu Fu3, Jing Nie5 and Chao Cheng1

1 Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China

2 Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA

3 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People’s Republic of China

4 Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, People’s Republic of China

5 Division of Nephrology, Nanfang Hospital, Guangzhou, Guangdong, People’s Republic of China

* These Authors contributed euqlly to this work

Correspondence:

Chao Cheng, email:

Jing Nie, email:

Liwu Fu, email:

Keywords: esophageal squamous cell carcinoma; ESCC; NUMB isoform 1; Aurora-A; G2/M arrest

Received: April 27, 2014 Accepted: June 24, 2014 Published: June 26, 2014

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.


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