Pin1 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma and Correlates With Poor Survival of Patients

J Biomed Sci. 2014 Aug 27;21(1):75. doi: 10.1186/s12929-014-0075-1.

Abstract

Background: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling. In this study, we investigated the involvement of Pin1 in tumor progression and in the prognosis of human esophageal squamous cell carcinoma (ESCC).

Results: We observed that proliferation, clonogenicity and tumorigenesis of CE81T cells were inhibited by Pin1 knockdown. We next analyzed Pin1 expression in clinical ESCC specimens. When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively. By immunohistochemistry, we identified that high Pin1 expression was associated with higher primary tumor stage (p = 0.035), higher overall cancer stage (p = 0.047) and poor overall survival (p < 0.001). Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D in cell line and clinical specimens was evaluated. β-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown. Cyclin D1 level correlated with Pin1 expression in clinical ESCC specimens.

Conclusions: Pin1 upregulation was associated with advanced stage and poor prognosis of ESCC. Pin1 knockdown inhibited aggressiveness of ESCC cells. β-catenin and cyclin D1 were positively regulated by Pin1. These results indicated that targeting Pin1 pathway could represent a potential modality for treating ESCC.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Disease-Free Survival
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Peptidylprolyl Isomerase / biosynthesis*
  • Peptidylprolyl Isomerase / genetics
  • Retrospective Studies
  • Survival Rate
  • Up-Regulation
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CCND1 protein, human
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neoplasm Proteins
  • beta Catenin
  • Cyclin D1
  • PIN1 protein, human
  • Peptidylprolyl Isomerase