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August 27, 2009

Hedgehog Pathway Found to Play Crucial Role in the Progression of Colon Cancer

  • A group of scientists report that blocking the hedgehog-GLI (HH-GLI) pathway can prevent the growth of colon cancer tumors, metastatic lesions, and cancer stem cells. Using cyclopamine, a naturally occurring chemical that inhibits HH-GLI, they were able to keep tumors from recurring in mice one year post-treatment.

    The HH-GLI signaling pathway is used by cells to communicate with each other, often to determine position, growth, and survival. “Previous work has hinted at the possible role of HH-GLI in colon cancer, but this was denied by other studies, so its involvement was never entirely clear,” states lead researcher, professor Ariel Ruiz i Altaba of Geneva University.

    “In this study we have proven that HH-GLI is essential for the development and growth of colon cancers. The research demonstrates the active presence of HH-GLI signaling in epithelial cells of colon cancers. Moreover, we found that metastatic tumors rely on this pathway for sustained growth.” The details appear in EMBO Molecular Medicine.

    “Recurrence is a major problem in cancer treatment,” Ruiz i Altaba continues. “While monitoring recovering mice we noted that tumors began to recur in all cases except for those treated with cyclopamine for a short period of time after tumor disappearance. The treated mice were kept for up to one year after the treatment and remained healthy and tumor free.”

    Methods to block HH-GLI activity also prevented cancer stem cell self renewal. Using a new in vivo assay to test the participation of cancer stem cells in a growing tumor, the research team demonstrated the essential role of this pathway for the maintenance and survival of cancer stem cells.


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