Hes1 Is Involved in the Self-Renewal and Tumourigenicity of Stem-Like Cancer Cells in Colon Cancer

Sci Rep. 2014 Feb 4;4:3963. doi: 10.1038/srep03963.

Abstract

A small subpopulation of cancer cells with stem cell-like features might be responsible for tumour generation, progression, and chemoresistance. Hes1 influences the maintenance of certain stem cells and progenitor cells and the digestive systems. We found upregulated Hes1 in poorly differentiated cancer samples compared with well-differentiated tumour samples, and most of the adenocarcinomas exhibited significantly higher levels of Hes1 mRNA compared with that observed in matched normal colon samples. Moreover, Hes1 expression was found to be correlated with the expression of stem cell markers in colon cancer samples, and Hes1 upregulates the expression of stemness-related genes in colon cancer cells. In addition, Hes1 enhances the self-renewal properties of the stem-like cells by increasing the sizes of CD133+ cells and SP cells and the ability of tumour sphere formation. Additionally, the Hes1-overexpressing cells formed significantly larger and higher number of colonies, as determined through the colony and the soft agar assays. More importantly, Hes1 enhances the tumourigenicity of colon cancer cell lines in nude mice and exhibits a strong tumour-formation ability at a cell density of 1 × 10(3). Taken together, our data indicate that Hes1 induces stem-like cell self-renewal and increases the number of tumour-initiating cells in colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Animals
  • Antigens, CD / metabolism
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / metabolism
  • HCT116 Cells
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / pathology*
  • Peptides / metabolism
  • RNA, Messenger / biosynthesis
  • Spheroids, Cellular
  • Transcription Factor HES-1
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • AC133 Antigen
  • Antigens, CD
  • Basic Helix-Loop-Helix Transcription Factors
  • Glycoproteins
  • Homeodomain Proteins
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • RNA, Messenger
  • Transcription Factor HES-1
  • HES1 protein, human