Non-Canonical Hh Signaling in Cancer—Current Understanding and Future Directions

Cancers

Dongsheng Gu²  Jingwu Xie¹ 

[1] Departments of Pediatrics, Biochemistry and Molecular Biology, Pharmacology and Toxicology, The Wells Center for Pediatrics Research, 1044 W, Walnut Street, Indianapolis, IN 46202, USA; E-Mail

关键词: hedgehog;    non-canonical;    smoothened;    Gli;   

DOI  :  10.3390/cancers7030857

来源: mdpi

【 摘 要 】

As a major regulatory pathway for embryonic development and tissue patterning, hedgehog signaling is not active in most adult tissues, but is reactivated in a number of human cancer types. A major milestone in hedgehog signaling in cancer is the Food and Drug Administration (FDA) approval of a smoothened inhibitor Vismodegib for treatment of basal cell carcinomas. Vismodegib can block ligand-mediated hedgehog signaling, but numerous additional clinical trials have failed to show significant improvements in cancer patients. Amounting evidence indicate that ligand-independent hedgehog signaling plays an essential role in cancer. Ligand-independent hedgehog signaling, also named non-canonical hedgehog signaling, generally is not sensitive to smoothened inhibitors. What we know about non-canonical hedgehog signaling in cancer, and how should we prevent its activation? In this review, we will summarize recent development of non-canonical hedgehog signaling in cancer, and will discuss potential ways to prevent this type of hedgehog signaling.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.