The influence of aberrant expression of GLI1/p-S6K on colorectal cancer

Biochem Biophys Res Commun. 2018 Sep 18;503(4):3198-3204. doi: 10.1016/j.bbrc.2018.08.124. Epub 2018 Aug 22.

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Recent studies have reported that PI3K/AKT/mTOR pathway regulated the GLI1 expression level via SMO-independent pathway in a variety of tumor types. We detected the expression level of GLI1/p-S6K in CRC tissues. We found the expression of GLI1/p-S6K was apparently close with lymph node metastasis and TNM stage and patients with positive GLI1/p-S6K expression had shorter survival time and patients with both GLI1 and p-S6K positive expression had an even worse overall survival than those with single positive expression. Moreover, GLI1 and p-S6K expression was considered to be independent prognostic factors in CRC patient and the positive co-expression of GLI1/p-S6K had greater influence than single expression positive on the prognosis of postoperative patients with tumor size≥5 cm, well differentiation, positive lymph node metastasis, venous invasion, neural invasion and TNM III-IV. Meanwhile, the GLI1/p-S6K expression had impact on more clinicopathologic features in colon-side carcinoma than in rectum-side carcinoma and the mTOR/S6K/GLI1 axis played an important role in CRC especially in advanced stage. Hence, further studies are underway to explore the molecular mechanism between GLI1 and p-S6K in CRC, and in addition, it offers novel facilities for molecular targeting therapy for CRC.

Keywords: Colorectal cancer; GLI1; Hedgehog; Prognosis; mTOR; p-S6K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Colon / pathology
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Rectum / pathology
  • Ribosomal Protein S6 Kinases / analysis*
  • Survival Analysis
  • Zinc Finger Protein GLI1 / analysis*

Substances

  • Biomarkers, Tumor
  • GLI1 protein, human
  • Zinc Finger Protein GLI1
  • Ribosomal Protein S6 Kinases