patched is a 12 pass transmembrane receptor: patched is the receptor for the key signaling protein...

By: Greg Stahr

PATCHEDAnd Its Role in Basal Cell Carcinoma

Patched is a 12 pass transmembrane receptor:

Patched is the receptor for the key signaling protein Hedgehog

In mammals Hedgehog signaling occurs through the cilium

PTCH is key at many places in normal development

Johnson, Milenkovic, et. Al. (Molecular Cell)

In Flies:• Anterior posterior patterning in

embryos• Wing Pattern

In Humans:• Somites• Neural tube• Brain Development

• Holoprosencephaly• Heart Development• Many other areas of the

body(http://en.wikipedia.org/wiki/Holoprosencephaly)

SHH Pathway is key in Nervous system patterning in Vertebrates

Basal Cell Carcinoma is the most common cancer in humans

(http://ghr.nlm.nih.gov/gene/PTCH1)

• Autosomal Dominant

• LOH at 9q22.3

(http://www.sciencedirect.com/science/article/pii/S1521661610000471)

(https://ufandshands.org/basal-cell-carcinoma)

Basal Cell Carcinoma affects the basal stem cells in the skin

Cyclopamine is a natural smoothened inhibitor

Vismodegib is another HH/PTCH1/SMO pathway inhibitor

• Typical treatment for BCCs is surgery • Inhibitor called Vismodegib shows promising results in clinical trials

Works Cited

• "Alkaloid." Wikipedia. Wikimedia Foundation, 04 Jan. 2013. Web. 01 Apr. 2013. <http://en.wikipedia.org/wiki/Alkaloid>.• "Basal Cell Carcinoma." UF&Shands, The University of Florida Academic Health Center. N.p., n.d. Web. 30 Mar. 2013. https://ufandshands.org/basal-cell-carcinoma.• Gailani, Mae R. “Developmental Genes and Cancer: Role of Patched in Basal Cell Carcinoma of the Skin”. Journal of National Cancer Institute. Vol. 89, No. 15, August 6, 1997• Gustafsson, Marcus K. “Myf is a direct target of long-range Shh signaling and Gli regulation for muscle specification”. Genes and Development. Vol 16. November 1, 2001.• "Holoprosencephaly." Wikipedia. Wikimedia Foundation, 29 Mar. 2013. Web. 30 Mar. 2013. <http://en.wikipedia.org/

wiki/Holoprosencephaly>.• Johnson RL., “In vivo functions of the patched protein”. Molecular Cell. Vol. 6, Issue 2, August 1, 2000• Nature.com. Nature Publishing Group, n.d. Web. 01 Apr. 2013

http://www.nature.com/nature/journal/v406/n6799/fig_tab/406944a0_ft.html.• "PTCH1." - Patched 1. N.p., n.d. Web. 30 Mar. 2013. http://ghr.nlm.nih.gov/gene/PTCH1.• Ribes, Vanessa; James Briscoe. “Establishing and Interpreting Graded Sonic Hedgehog Signaling during Vertebrate Neural

Tube Patterning”. Cold Spring Harbor Perspectives in Biology (2009). July 15, 2009.• Robbins, David J., “The Hedgehog Signal Transduction Network”. Cell Biology. Vol. 5, Issue 246, October 16, 2011• Tang, Jean Y., et al. “Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome”. The New England Journal of Medicine. Vol 366. June 7, 2012.• "What Are Basal and Squamous Cell Skin Cancers?" What Are Basal and Squamous Cell Skin Cancers? N.p., n.d. Web. 30 Mar. 2013. <http://www.cancer.org/cancer/skincancer-basalandsquamouscell/detailedguide/skin-cancer-basal-and-squamous-cell-what-is-basal-and-squamous-cell>.