title: The implications and mechanisms of the extra-nuclear nucleolin in the esophageal squamous cell carcinomas.
abstract: In recent decades, the multi-functional protein nucleolin (NCL) has been reported to express outside the nucleus of many cancer cells. However, the expression and role of the extra-nuclear NCL in esophageal squamous cell carcinoma (ESCC) were not well characterized. Here, NCL was detected by immunohistochemistry and Western blotting in 60 ESCC tissues. Further, the associations of NCL, EGFR, CXCR4 and Ki67 were analyzed by in vitro assays. Our results showed that NCL expression in all 40 cases of ESCC tissues with metastasis was extensively located in the nucleus, cytoplasm and cell membrane (extra-nucleus), while NCL expression in all 20 cases of ESCC without metastasis was merely limited into the nucleus (intra-nucleus).The extra-nuclear NCL expression was positively correlated with the expression of EGFR, CXCR4 and Ki67 and serves as an independent prognostic factor for ESCC patients. In vitro, NCL siRNA (si-NCL) efficaciously affected the expression of EGF or SDF-1-induced p-AKT, p-ERK and Ki67. Also, NCL siRNA inhibited the capacity of migration and invasion of ECA109 cells. In conclusions, our study suggests that NCL is implicated in the initiation and transduction of EGFR and CXCR4 signaling and further up-regulates Ki67 expression to modulate the biological behaviors of ESCC. Clinically, the extra-nuclear NCL expression can be used as an important indicator to determine metastasis and predict the prognosis, which help develop new therapeutic strategies against ESCC.
authors: Nan Fang Hospital, Southern Medical University, Guangzhou, China.
authors: Jiafeng
authors: J
authors: Qi
authors: Huiling
authors: H
authors: Li
authors: Nanbo
authors: N
authors: Liu
authors: Yutong
authors: Y
authors: Xing
authors: Gang
authors: G
authors: Zhou
authors: Yao
authors: Y
authors: Wu
authors: Yuanhang
authors: Y
authors: Liu
authors: Wenxia
authors: W
authors: Chen
authors: Jie
authors: J
authors: Yue
authors: Bater
authors: B
authors: Han
authors: Shirong
authors: S
authors: Kang
authors: Xu
authors: X
authors: Wu
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D000097796:Nucleolin
chemical_list: D066246:ErbB Receptors; D019394:Ki-67 Antigen; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D019718:Receptors, CXCR4; D000097796:Nucleolin; C527276:CXCR4 protein, human; C512478:EGFR protein, human
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