title: The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma.
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.
authors: Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. These Authors contributed euqlly to this work.
authors: Junmou
authors: J
authors: Hong
authors: Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. These Authors contributed euqlly to this work.
authors: Zhenguo
authors: Z
authors: Liu
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Hua
authors: H
authors: Zhu
authors: Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Xin
authors: X
authors: Zhang
authors: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Yongju
authors: Y
authors: Liang
authors: Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Shiyuan
authors: S
authors: Yao
authors: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Fang
authors: F
authors: Wang
authors: Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, People's Republic of China.
authors: Xiaoyun
authors: X
authors: Xie
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Bo
authors: B
authors: Zhang
authors: Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Tao
authors: T
authors: Tan
authors: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Liwu
authors: L
authors: Fu
authors: Division of Nephrology, Nanfang Hospital, Guangzhou, Guangdong, People's Republic of China.
authors: Jing
authors: J
authors: Nie
authors: Department of Thoracic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Chao
authors: C
authors: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D020033:Protein Isoforms