Hedgehog signalling in colorectal tumour cells: induction of apoptosis with cyclopamine treatment

Int J Cancer. 2004 Jul 20;110(6):831-7. doi: 10.1002/ijc.20227.


Hedgehog (Hh) signalling controls many aspects of development. It also regulates cell growth and differentiation in adult tissues and is activated in a number of human malignancies. Hh and Wnt signalling frequently act together in controlling cell growth and tissue morphogenesis. Despite the fact that the majority of colorectal tumours have a constitutively activated canonical Wnt pathway, few previous studies have investigated the expression of Hh signalling components in colorectal tumours. We describe here epithelial cell lines derived from both nonmalignant colorectal adenomas and colorectal adenocarcinomas that express both Sonic and Indian Hh. Interestingly, these cells also express the Hh receptor Patched and the downstream signalling components Smoothened and Gli1, suggesting autocrine Hh signalling in these cells. To test whether autocrine Hh signalling contributes to cell survival, we treated colorectal tumour cells with cyclopamine, a known inhibitor of Hh signalling. Cyclopamine treatment induced apoptosis in both adenoma- and carcinoma-derived cell lines, which could be partially rescued by further stimulation of Hh signalling. These data suggest that autocrine Hh signalling can increase aberrant cell survival in colorectal tumour cells and may be a novel target for colon cancer therapy using drugs such as cyclopamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma
  • Apoptosis / drug effects*
  • Carcinoma
  • Cell Line, Tumor
  • Colonic Neoplasms / pathology*
  • DNA Primers
  • Hedgehog Proteins
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology
  • Rectal Neoplasms / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Veratrum Alkaloids / pharmacology*
  • Wnt Proteins


  • DNA Primers
  • Hedgehog Proteins
  • Proto-Oncogene Proteins
  • SHH protein, human
  • Trans-Activators
  • Veratrum Alkaloids
  • Wnt Proteins
  • cyclopamine