Vertebrate Hedgehog (Hh) signals involved in development and some forms of cancer, such as basal cell carcinoma, are transduced by the primary cilium, a microtubular projection found on many cells. A critical step in vertebrate Hh signal transduction is the regulated movement of Smoothened (Smo), a seven-transmembrane protein, to the primary cilium. To identify small molecules that interfere wi...

Smoothened (Smo) is a member of the Frizzled (FzD) class of G-protein-coupled receptors (GPCRs), and functions as the key transducer in the Hedgehog (Hh) signalling pathway. Smo has an extracellular cysteine-rich domain (CRD), indispensable for its function and downstream Hh signalling. Despite its essential role, the functional contribution of the CRD to Smo signalling has not been clearly elu...

ates Ptc from Smo (Figure 1B) is also generally enter-Daniel Kalderon* tained (Chen and Struhl, 1996) because it is countered Department of Biological Sciences only by a single observation of Ptc-mediated binding of Columbia University Hh to Smo in tissue culture cells that expressed high New York, New York 10027 levels of both vertebrate Ptc and Smo (Stone et al., 1996). Some new data support ...

Previous studies report controversial role of Hedgehog (HH) signaling in the progression of colon cancer. This study aimed to investigate the expressions of smoothened (SMO) and downstream glioma-associated oncogene homology-1 (GLI1) in colon cancer, colonic adenoma and normal tissues. Colon cancer and normal tissue samples were collected from 49 patients with colon cancer while colonic adenoma...

absence of Hh ligand, Ptc restrains Smo activity ; binding of Hh to Ptc releases Smo, which then transmits the intracellular signal. The regulation of Smo activity therefore occupies a pivotal position in the cellular response to Hh. Previous work had identified small molecules that inhibit or activate Hh signaling by interacting with Smo 6–8. These include the antagonist cyclopamine as well as...

BACKGROUND Few studies have associated microRNAs (miRNAs) with the hedgehog (Hh) pathway. Here, we investigated whether targeting smoothened (SMO) with miR-326 would affect glioma biological behavior and stemness. METHODS To investigate the expression of SMO and miR-326 in glioma specimens and cell lines, we utilized quantitative real-time (qRT)-PCR, Western blot, immunohistochemistry, and fl...

Hedgehog (Hh) signaling is essential for normal growth, patterning, and homeostasis of many tissues in diverse organisms, and is misregulated in a variety of diseases including cancer. Cytoplasmic Hedgehog signaling is activated by multisite phosphorylation of the seven-pass transmembrane protein Smoothened (Smo) in its cytoplasmic C-terminus. Aside from a short membrane-proximal stretch, the s...

Hedgehog (HH) pathway Smoothened (Smo) inhibitors are active against Gorlin syndrome-associated basal cell carcinoma (BCC) and medulloblastoma where Patched (Ptch) mutations occur. We interrogated 705 epithelial cancer cell lines for growth response to the Smo inhibitor cyclopamine and for expressed HH pathway-regulated species in a linked genetic...

MicroRNA (miR)-20a, a member of the miR-17-92 cluster related to cardiac development, was obviously downregulated in myocardially differentiated P19 cells compared with normal P19 cells. Smoothened (SMO) is a member of the Hh pathway. Hh signaling induces cardiac differentiation in P19 cells, and SMO mediates the Hh pathway during embryonic development. Using bioinformatic prediction software T...

A new approach to measure muscle oxygen saturation (SmO(2)) using near infrared spectroscopy (NIRS) has been proposed in this paper. This approach exploits the cyclic NIRS signals seen during exercise which are often regarded as "movement artefacts". This new measure, which we term the "cyclic SmO(2)", has the potential to be less affected by the myoglobin which is traditionally believed to be ...