Expression and clinical significance of SALL4 and β-catenin in colorectal cancer

J Mol Histol. 2016 Apr;47(2):117-28. doi: 10.1007/s10735-016-9656-5. Epub 2016 Jan 16.

Abstract

Previous studies on the expression of Sal-like 4 (SALL4), a zinc finger transcription factor, had conflicting results in colorectal cancer (CRC). The main aim of this study was to investigate the expression of SALL4 and its relationship with β-catenin in CRC. Immunohistochemistry was performed to examine the expression of SALL4 and β-catenin in a cohort of 149 patients with CRC, 12 with atypical hyperplasia, 25 with benign tumor and 38 with normal tissue. Expression patterns of SALL4 and β-catenin and correlation with clinicopathological features were investigated. The relationship between SALL4 and β-catenin was examined by immunofluorescence and co-immunoprecipitation using CRC cell lines, SW480, SW620, HCT116 and HT29. Immunohistochemical analysis revealed significantly lower expression of SALL4 in CRC (46.3 %) than atypical hyperplasia (68.0 %, p < 0.05) and normal tissue (78.9 %, p < 0.01). Well-differentiated CRC seemed to express more SALL4 (47.6 %) than moderately (45.8 %) and poorly-differentiated cancers (18.8 %) (p < 0.05). However, SALL4 expression positively correlated with lymph node metastasis and tumor-node-metastasis (TNM) and Dukes stages (all p < 0.05) suggesting a new mechanism involved in the function of SALL4 in CRC. β-catenin was expressed significantly higher in CRC (69.1 %) than normal tissue (21.1 %, p < 0.01), and positively correlated with CA19-9 level in serum (p < 0.05). SALL4 and β-catenin were positively correlated in CRC (Spearman correlation coefficient R = 0.536, p < 0.01). The group of co-expression of the two molecules showed advanced lymph node metastasis, TNM stage and Dukes stage (all p < 0.05). Double-labeling immunofluorescence and co-immunoprecipitation indicated that SALL4 and β-catenin co-localized in the nucleus and cytoplasm and interacted. Taken together, our results revealed that SALL4 and β-catenin were positively correlated in CRC. In CRC cells, SALL4 and β-catenin co-localized and interacted. The function of SALL4 in promoting lymph node metastasis and advanced clinical stage might partly be due to the interaction with β-catenin.

Keywords: Co-localization; Colorectal cancer; Immunohistochemistry; Interaction; SALL4; β-Catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Male
  • Middle Aged
  • Prognosis
  • Transcription Factors / metabolism*
  • beta Catenin / metabolism*

Substances

  • SALL4 protein, human
  • Transcription Factors
  • beta Catenin