title: Increased Numb protein expression predicts poor clinical outcomes in esophageal squamous cell carcinoma patients.
abstract: 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.
authors.affiliation: a Department of Thoracic Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: b Department of Pathology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Canqiao
authors.initials: C
authors.lastname: Luo
authors.affiliation: a Department of Thoracic Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Weixiong
authors.initials: W
authors.lastname: Yang
authors.affiliation: c State Key Laboratory of Oncology in South China , Cancer Center, Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Kefeng
authors.initials: K
authors.lastname: Wang
authors.affiliation: a Department of Thoracic Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Hu
authors.affiliation: a Department of Thoracic Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Zou
authors.affiliation: d Department of Surgery , Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center , Columbus , OH , USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: c State Key Laboratory of Oncology in South China , Cancer Center, Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Liwu
authors.initials: L
authors.lastname: Fu
authors.affiliation: e Division of Nephrology , Nanfang Hospital , Guangzhou , P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: a Department of Thoracic Surgery , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016629:Esophagectomy; D004947:Esophagus / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D002945:Cisplatin
keywords: Apoptosis; ESCC; Numb protein; cancer stem cell; esophageal squamous cell carcinoma; prognosis; proliferation