Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling

• DOI: 10.1073/pnas.0404956101
• Publication Date: 2004-08-17T01:08:46Z
• Authors: Pilar Sanchez; Ana Maria Hernández; Barbara Stecca; Andrea J. Kahler; Amy M. DeGueme; Andrea Barrett; Mercedes Beyna; Milton W. Datta; Sumana Datta; Ariel Ruiz i Altaba
• Keywords: Cyclopamine; GLI1; DU145

Prostate cancer is the most common solid tumor in men, and it shares with all cancers hallmark of elevated, nonhomeostatic cell proliferation. Here we have tested hypothesis that SONIC HEDGEHOG (SHH)–GLI signaling pathway implicated prostate cancer. We report expression SHH–GLI components adult human cancer, often enhanced levels tumors versus normal prostatic epithelia. Blocking cyclopamine or anti-SHH antibodies inhibits proliferation GLI1 + / PSA primary cultures. Inversely, SHH can potentiate proliferation, suggesting autocrine may sustain growth. In addition, blockade three metastatic lines through RNA interference leads to inhibition cell-autonomous activation at different showing an essential role for cells. Our data demonstrate dependence on function suggest a novel therapeutic approach.