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Review
. 2020 Apr;10(2):233-248.
doi: 10.1007/s13555-020-00355-1. Epub 2020 Jan 29.

Clinical Implications of Primary Cilia in Skin Cancer

Abrar Choudhury  1   2 , Neil M Neumann  3 , David R Raleigh  1   2 , Ursula E Lang  4   5
Affiliations
Review

Clinical Implications of Primary Cilia in Skin Cancer

Abrar Choudhury et al. Dermatol Ther (Heidelb). 2020 Apr.

Abstract

The primary cilium is a cell surface organelle that is an important component of cellular biology. While it was once believed to be a vestigial structure without biologic function, it is now known to have essential roles in critical cellular signaling pathways such as Hedgehog (HH) and Wnt. The HH and Wnt pathways are involved in pathogenesis of basal cell carcinoma and melanoma, respectively, and this knowledge is now beginning to inform therapeutic and diagnostic options for patients. The purpose of this review is to familiarize clinicians with primary cilia biology and how this complex cellular organelle has started to translate into clinical care.

Keywords: Basal cell carcinoma; Diagnostic tool; Hedgehog; Melanoma; Primary cilia; Sonidegib; Vismodegib.

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Conflict of interest statement

Abrar Choudhury, Neil M. Neumann, David R. Raleigh, and Ursula E. Lang have nothing to disclose.

Figures

Fig. 1
Fig. 1
Immunofluorescence staining and structure of primary cilia. a Immunofluorescence staining of primary cilia on basal cell carcinoma is shown (scale bar 50 µm). Nuclei are highlighted in blue (DAPI), the ciliary axoneme is shown in green (acetylated alpha-tubulin), and centrioles are displayed in red (gamma-tubulin). b Unlike motile cilia, only one primary cilium is present per cell, and the primary cilium’s axoneme does not contain central microtubule singlets nor dynein arms
Fig. 2
Fig. 2
Timeline of major contributions to the cilia literature
Fig. 3
Fig. 3
Hedgehog pathway activation through the primary cilium. When the Hedgehog pathway is off, patched (PTCH1) localizes to the primary cilium and prevents Smoothened (SMO) from entering the cilium. Simultaneously, suppressor of fused homolog (SUFU) binds to and inhibits the activity of glioma-associated oncogene homolog (GLI) transcription factors. Hedgehog ligands (HH) activate the pathway by binding to PTCH1, causing it to leave the cilium, and allowing SMO to enter. SMO in turn activates GLI proteins, allowing for the transcription of Hedgehog target genes
Fig. 4
Fig. 4
Primary cilia immunofluorescence staining in melanocytic nevus and melanoma. Immunofluorescence staining shows melanocyte nuclei highlighted blue (SOX-10), ciliary axoneme shown in green (acetylated alpha-tubulin), and centrioles in red (gamma-tubulin). For the purpose of quantification for calculation of the ciliation index (% ciliated lesional melanocytes), a cell is considered positive if it contains an elongated ciliary axoneme extending from a centriole and negative if only centrioles are identified. Only melanocytes with identifiable centrioles are counted in at least three high-power fields, with an overall minimum of 150 melanocytes. An example of the immunofluorescence and corresponding hematoxylin and eosin (H&E) stains are shown for a melanocytic nevus (a) and invasive melanoma (b) (scale bar 50 µm)
See this image and copyright information in PMC

References

    1. Satir P, Christensen ST. Overview of structure and function of mammalian cilia. Annu Rev Physiol. 2007;69:377–400. doi: 10.1146/annurev.physiol.69.040705.141236. - DOI - PubMed
    1. Seeley ES, Nachury MV. The perennial organelle: assembly and disassembly of the primary cilium. J Cell Sci. 2010;123(Pt 4):511–518. doi: 10.1242/jcs.061093. - DOI - PMC - PubMed
    1. Oh EC, Katsanis N. Context-dependent regulation of Wnt signaling through the primary cilium. J Am Soc Nephrol. 2013;24(1):10–18. doi: 10.1681/ASN.2012050526. - DOI - PubMed
    1. Goetz SC, Anderson KV. The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet. 2010;11(5):331–344. doi: 10.1038/nrg2774. - DOI - PMC - PubMed
    1. Nielsen BS, Malinda RR, Schmid FM, Pedersen SF, Christensen ST, Pedersen LB. PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism. J Cell Sci. 2015;128(19):3543–3549. - PubMed