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Cathepsin B is a target of Hedgehog signaling in pancreatic cancer

Jin-Hyeok Hwang1, Sang Hyub Lee, Kwang Hyuck Lee

  • 1Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungon-dong Chongno-gu, Seoul 110-744, Republic of Korea.

Cancer Letters
|November 14, 2008
PubMed

Insights

Hedgehog signaling influences pancreatic cancer by targeting cathepsin B. Inhibiting this pathway reduces cancer cell invasiveness, suggesting a potential therapeutic target for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Pancreatic cancer is a complex disease with limited treatment options.
  • Hedgehog (Hh) signaling pathway plays a role in cancer development and progression.
  • Cathepsin B (CATB) is implicated as a downstream target in various cancers.

Purpose of the Study:

  • To investigate the role of cathepsin B (CATB) as a downstream target of Hedgehog (Hh) signaling in pancreatic cancer.
  • To determine the effect of Hh signaling inhibition on CATB expression and pancreatic cancer cell behavior.

Main Methods:

  • Utilized PANC-1, a Shh-positive pancreatic cancer cell line.
  • Administered Cyclopamine, an Hh signal inhibitor.
  • Performed microarray analysis to identify Hh-regulated genes.
  • Assessed CATB protein and mRNA levels.
  • Evaluated the impact of Cyclopamine and CATB inhibitor on cell invasiveness.
  • Correlated CATB expression with Shh expression in human pancreatic cancer tissues.

Main Results:

  • Cyclopamine suppressed Shh and Gli1 expression, inducing apoptosis in PANC-1 cells.
  • Microarray analysis identified CATB as downregulated by Hh signaling.
  • Cyclopamine treatment reduced both protein and mRNA levels of CATB.
  • Inhibition of Hh signaling or CATB significantly reduced PANC-1 cell invasiveness (P<0.05).
  • CATB expression showed a trend towards correlation with Shh expression in patient tissues (P=0.053).

Conclusions:

  • Hedgehog signaling pathway directly targets and downregulates cathepsin B expression.
  • Hedgehog signaling, potentially through cathepsin B, influences pancreatic cancer cell invasiveness.
  • Targeting the Hh-CATB axis presents a potential therapeutic strategy for pancreatic cancer.

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