Downregulation of Beclin 1 and impairment of autophagy in a small population of colorectal cancer

Dig Dis Sci. 2013 Oct;58(10):2887-94. doi: 10.1007/s10620-013-2732-8. Epub 2013 Jun 29.

Abstract

Background: Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has been observed in most colorectal cancer tissues. However, there is a small population of colorectal cancers with downregulation of Beclin 1.

Aim: The purpose of this study was to investigate the role autophagy plays in colorectal cancers with downregulation of Beclin 1.

Methods: LC3 protein, an autophagosome marker, was assessed by ICH and WB in colorectal cancers tissues. An anti-tumor effect of Beclin 1 was examined by introducing exogenous Beclin 1 in vitro. Colony formation assay, growth curves and mouse xenograft were analysed.

Results: Our results showed that LC3 was suppressed in the colorectal cancers (9.86 %) with downregulation of Beclin 1. Moreover, overexpression of Beclin 1 inhibited colorectal cancer cell growth and enhanced the rapamycin-induced antitumor effect in vitro.

Conclusion: Downregulation of Beclin 1 and autophagy inhibition play an important role in a part of colorectal cancers. Activating autophagy or overexpression of Beclin 1 may be an effective treatment for some colorectal cancers. Detection of expression profile of Beclin 1 in colorectal cancers could be a strategy for new diagnostic and therapeutic methods.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / physiopathology*
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis Regulatory Proteins / pharmacology
  • Autophagy / physiology*
  • Beclin-1
  • Biomarkers / metabolism
  • Carcinogenesis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology*
  • Down-Regulation / physiology*
  • Female
  • HT29 Cells
  • Humans
  • In Vitro Techniques
  • Membrane Proteins / metabolism*
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Nude
  • Microtubule-Associated Proteins / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Biomarkers
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins