Contributed by Allison A. Curley, PhD
The Hedgehog (Hh) signaling pathway is very active during early embryonic development, where it is essential for tissue patterning and organogenesis, but is largely silent during adulthood. Mammals have three secreted Hh ligands: sonic (Shh), indian (Ihh), and desert Hh (Dhh). Additional downstream components of the pathway include the transmembrane receptors, Patched (Ptch) and Smoothened (Smo), which eventually culminate in the activation of glioma-associated oncogene (GLI) transcription factors.1
Dysregulation of the Hh pathway has been linked to several types of cancer. Somatic mutations in Ptch are present in over 90% of sporadic basal cell carcinoma cases and in about a fifth of medulloblastoma brain tumors.2,3 In addition, large-scale, whole-genome and whole-exome studies have linked extremely rare Ptch mutations with many other cancers. Mutations leading to increased activity of Smo and GLI are also implicated in carcinogenesis.4 In contrast to these ligand-independent mechanisms of tumor formation, the Hh molecule itself is also thought to play a role. One hypothesized mechanism involves tumor cell secretion of Hh into the local environment, which in turn stimulates further tumor growth.1 Another ligand-dependent mechanism is thought to involve Hh’s maintenance and differentiation of cancer stem cells.5
Blocking Hh signaling for therapeutic purposes has been the subject of a great deal of research. Drugs that inhibit the function of SMO, affect the binding between Hh and Ptch, or repress GLI have all been tested, with varied results. One such SMO inhibitor, vismodegib, is now approved for the treatment of basal cell carcinoma.6 However, many SMO inhibitor trials in other types of cancer have been negative, underscoring the need for future research on Hh signaling.4
Detection of human TRIP1(SUG1) in FFPE metastatic lymph node from lung carcinoma by IHC. Antibody: Rabbit anti-TRIP1(SUG1) (A300-791A). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.
Below is the entire list of targets involved in hedgehog signaling. Can’t find what you are looking for? Bethyl offers a custom antibody service.