title: STMN-1 is a potential marker of lymph node metastasis in distal esophageal adenocarcinomas and silencing its expression can reverse malignant phenotype of tumor cells.
abstract: BACKGROUND
  Distal esophageal adenocarcinoma is a highly aggressive neoplasm. Despite advances in diagnosis and therapy, the prognosis is still poor. Stathmin (STMN-1) is a ubiquitously expressed microtubule destabilizing phosphoprotein. It promotes the disassembly of microtubules and prevents assembly. STMN-1 can cause uncontrolled cell proliferation when mutated and not functioning properly. Recently, found to be overexpressed in many types of human cancers. However, its clinical significance remains elusive in distal esophageal adenocarcinoma. Here, we reported for the first time that STMN-1 is highly overexpressed in adenocarcinomas of the distal esophagus and strongly associated with lymph node metastasis.
  
  
  METHODS
  STMN-1 expression in 63 cases of distal esophageal adenocarcinoma was analyzed by immunoblotting, while expression in esophageal adenocarcinoma cells was determined by immunocytochemistry, immunofluorescence, qRT-PCR and western blotting. Lentivirus-mediated RNAi was employed to knock-down STMN-1 expression in Human esophageal adenocarcinoma cells. The relationship between STMN-1 expression and lymph node metastasis in distal esophageal adenocarcinoma was determined by univariate and multivariate analyses.
  
  
  RESULTS
  STMN-1 was detected in 31 (49.21%) of the 63 cases. STMN-1 was highly overexpressed in specimens with lymph node metastasis pN (+), but its expression was almost undetected in pN (-) status. Multivarian regression analysis demonstrated that STMN-1 overexpression is an independent factor for lymph node metastasis in distal esophageal adenocarcinoma. STMN-1 shRNA effectively reduced STMN-1 expression in esophageal adenocarcinoma cells (P < 0.05), which significantly suppressed proliferation (P < 0.05), increased migration (P < 0.05) and invasion ability (P < 0.05) and G1 phase arrest (P < 0.05) which lead to induction of apoptosis in esophageal adenocarcinoma cells in vitro. To verify the in vitro data, we conducted in vivo tumor xenograft studies. Esophageal adenocarcinoma cells stably transfected with STMN-1 shRNA significantly reduced tumor xenografts volume in vivo.
  
  
  CONCLUSIONS
  STMN-1 overexpression is associated with lymph node metastasis and increase malignancy in distal esophageal adenocarcinoma. In vivo and in vitro laboratory findings, suggests that STMN-1 may be a suitable target for future therapeutic strategies in distal esophageal adenocarcinoma.
authors.forename: Javed
authors.initials: J
authors.lastname: Akhtar
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
authors.forename: Che
authors.initials: C
authors.lastname: Yu
authors.forename: Chen-Sheng
authors.initials: CS
authors.lastname: Li
authors.affiliation: Division of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong University, 250021 Shandong, China. shiyl9889@126.com.
authors.forename: Yu-Long
authors.initials: YL
authors.lastname: Shi
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C493995:STMN1 protein, human; D050777:Stathmin