RACK1 predicts poor prognosis and regulates progression of esophageal squamous cell carcinoma through its epithelial-mesenchymal transition

Cancer Biol Ther. 2015;16(4):528-40. doi: 10.1080/15384047.2015.1016687. Epub 2015 Feb 26.

Abstract

Background: RACK1 is known to be involved in tumor progression, and its prognostic value on many kinds of tumors has been identified. However, there are limited studies about the functional role of RACK1 in esophageal squamous cell carcinoma (ESCC).

Patients and methods: RACK1 expression was examined in 100 ESCC tissue samples using immunohistochemistry staining. RACK1 was knocked-down in ESCC cell lines by shRNA. The effects on cell proliferation, invasion and migration were examined in ESCC cell lines and nude mouse model. Vimentin and E-cadherin were introduced to further study the association between RACK1 and EMT.

Results: RACK1 expression was significantly associated with the tumor length (P = 0.012), diameter<3 cm (P = 0.047), T stage (P = 0.032), and lymph node metastasis (P = 0.038), respectively. Kaplan-Meier survival analysis and Cox analyses revealed RACK1 expression was an independent predictor for OS (P = 0.030) and DFS (P = 0.027) in ESCC. Down-regulation of RACK1 inhibited cell proliferation, along with invasion and migration in vitro and in vivo. A significant positive correlation between RACK1 expression and vimentin (P = 0.0190) and an inverse correlation between RACK1 expression and E-cadherin (P = 0.0047) were found.

Conclusions: RACK1 predicted poor prognosis in ESCC, promoted tumor progression, and was involved in EMT of ESCC.

Keywords: C, chemotherapy; CRT, chemoradiotherapy; DFS, disease-free survival; EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; F, female; IHC, immunohistochemistry; M, male; OS, overall survival; R, radiotherapy; RACK1; RACK1, Receptor for Activated C Kinase 1; epithelial-mesenchymal transition; esophageal squamous cell carcinoma; prognosis; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Cadherins / genetics
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • GTP-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Prognosis
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface / genetics*
  • Vimentin / pharmacology

Substances

  • Biomarkers, Tumor
  • Cadherins
  • Neoplasm Proteins
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • Receptors, Cell Surface
  • Vimentin
  • GTP-Binding Proteins