Mutated genes in cancer (41) – SMO

SMO

In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 6608 or SMO

● Ensembl (http://www.ensembl.org/index.html): ENSG00000128602

● UniProt (http://www.uniprot.org/): Q99835

● OMIM (http://www.ncbi.nlm.nih.gov/omim): 601500

● GeneCards (http://www.genecards.org/): SMO

● HGNC (http://www.genenames.org/): 11119 or SMO

Gene locus:

7q32.1

Protein name:

Smoothened homolog (Drosophila)

Protein Size:

787 amino acids; about 86 kDa

Function:

The Hedgehog signalling pathway controls numerous developmental processes. In response to Hedgehog, Smoothened (Smo), a seven-pass transmembrane protein, orchestrates pathway signalling and controls transcription factor activation. In the absence of Hedgehog, the receptor Patched indirectly inhibits Smo in a catalytic manner. Many questions surrounding Smo activation and signalling remain. Recent findings in Drosophila and vertebrate systems have provided strong evidence that Smo acts as a G-protein-coupled receptor (Ayers KL, Thérond PP. 2010).

Cancer-related alterations:

Somatic SMO mutations have been found in biliary tract (about 10% of cases), skin, large intestine, upper aerodigestive tract and liver tumors. There are no mutational hot spots. Alterations are mostly substitutions.

Therapy:

Cyclopamine (Cyc), an alkaloid from the Veratrum plant, is a specific natural product inhibitor of the Hedgehog pathway that acts by targeting smoothened (SMO) protein. However, its poor solubility, acid sensitivity, and weak potency relative to other Hedgehog antagonists prevent the clinical development of Cyc as a therapeutic agent (Fan Q. et al. 2011).

References (open access):

Constitutive activation of smoothened (SMO) in mammary glands of transgenic mice leads to increased proliferation, altered differentiation and ductal dysplasia. Moraes RC, Zhang X, Harrington N, Fung JY, Wu MF, Hilsenbeck SG, Allred DC, Lewis MT. Development. 2007 Mar;134(6):1231-42.

http://dev.biologists.org/content/134/6/1231.long

Tumor shrinkage by cyclopamine tartrate through inhibiting hedgehog signaling. Fan Q, Gu D, He M, Liu H, Sheng T, Xie G, Li CX, Zhang X, Wainwright B, Garrossian A, Garrossian M, Gardner D, Xie J. Chin J Cancer. 2011 Jul;30(7):472-81.

http://www.cjcsysu.cn/ENpdf/2011/7/472.pdf