A loss-of-function mutation in PTCH1 suggests a role for autocrine hedgehog signaling in colorectal tumorigenesis

作者：Chung Jon H; Bunz Fred^*

来源：Oncotarget, 2013, 4(12): 2208-2211.

• Hedgehog
• colorectal cancer
• Patched
• vismodegib
• autocrine

Hedgehog (Hh) signaling is largely suppressed in the normal differentiated tissues of the adult but activated in many cancers. The Hh pathway can either be activated by the expression of Hh ligands, or by mutations that cause constitutive, ligand-independent signaling. Colorectal cancer cells frequently express Hh ligands that are believed to exert paracrine effects on the stromal component of the tumor. Evidence for a more direct role of Hh signaling on the growth and evolution of colorectal cancer cell clones has been lacking. Here, we report a loss-of-function mutation of PTCH1, a tumor suppressor in the Hh pathway, in a colorectal cancer that exhibits transcriptional upregulation of the downstream Hh gene GLI1. This finding demonstrates that autocrine Hh signaling can provide a selective advantage to evolving tumors that arise in the colorectal epithelia, and suggests a definable group of colorectal cancer patients that could derive enhanced benefit from Hh pathway inhibitors.

• 出版日期2013-12