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The Role of Patched Receptor in Basal Cell Carcinoma Development

The Patched (PTCH) protein is a crucial 12-pass transmembrane receptor involved in the Hedgehog signaling pathway, which plays a significant role in various developmental processes in both flies and humans. This pathway is critical for nervous system patterning in vertebrates. Basal cell carcinoma (BCC) is the most common cancer in humans, primarily affecting basal skin stem cells. Treatment includes surgical options and inhibitors like Vismodegib, which shows promising results. Understanding the PTCH receptor's function may enhance therapeutic strategies for BCC management.

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The Role of Patched Receptor in Basal Cell Carcinoma Development

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  1. PATCHED And Its Role in Basal Cell Carcinoma By: Greg Stahr

  2. Patched is a 12 pass transmembrane receptor:

  3. Patched is the receptor for the key signaling protein Hedgehog

  4. In mammals Hedgehog signaling occurs through the cilium

  5. PTCH is key at many places in normal development • In Flies: • Anterior posterior patterning in embryos • Wing Pattern Johnson, Milenkovic, et. Al. (Molecular Cell) • In Humans: • Somites • Neural tube • Brain Development • Holoprosencephaly • Heart Development • Many other areas of the body (http://en.wikipedia.org/wiki/Holoprosencephaly)

  6. SHH Pathway is key in Nervous system patterning in Vertebrates

  7. Basal Cell Carcinoma is the most common cancer in humans • Autosomal Dominant (http://www.sciencedirect.com/science/article/pii/S1521661610000471) • LOH at 9q22.3 (http://ghr.nlm.nih.gov/gene/PTCH1)

  8. Basal Cell Carcinoma affects the basal stem cells in the skin (https://ufandshands.org/basal-cell-carcinoma)

  9. Cyclopamine is a natural smoothened inhibitor

  10. Vismodegib is another HH/PTCH1/SMO pathway inhibitor • Typical treatment for BCCs is surgery • Inhibitor called Vismodegib shows promising results in clinical trials

  11. 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>.

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