Skip to main content
Open Access Publications from the University of California


UC San Francisco Previously Published Works bannerUCSF

Targeting the metabolic pathway of human colon cancer overcomes resistance to TRAIL-induced apoptosis.

  • Author(s): Carr, Ryan M
  • Qiao, Guilin
  • Qin, Jianzhong
  • Jayaraman, Sundararajan
  • Prabhakar, Bellur S
  • Maker, Ajay V
  • et al.

Colon cancer is a leading cause of cancer-related mortality for which targeted therapy is needed; however, trials using apoptosis-inducing ligand monotherapy to overcome resistance to apoptosis have not shown clinical responses. Since colon cancer cells selectively uptake and rapidly metabolize glucose, a property utilized for clinical staging, we investigated mechanisms to alter glucose metabolism in order to selectively target the cancer cells and to overcome evasion of apoptosis. We demonstrate TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) resistance in the majority of human colon cancers tested and utilize the glucose analog 2-deoxy-d-glucose to sensitize TRAIL-resistant gastrointestinal adenocarcinoma cells, and not normal gastrointestinal epithelial cells, to TRAIL-induced apoptosis through enhanced death receptor 5 expression, downstream modulation of MAPK signaling and subsequent miRNA expression modulation by increasing the expression of miR-494 via MEK activation. Further, established human colon cancer xenografts treated with this strategy experience anti-tumor responses. These findings in colon adenocarcinoma support further investigation of manipulation of cellular energetics to selectively overcome resistance to apoptosis and to impart tumor regressions in established colon cancer tumors.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View