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Nevogenesis pp 117–126Cite as

Nevus Senescence: An Update

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Abstract

Nevi and melanomas share the many of the same growth-promoting mutations. However, benign nevi eventually undergo growth arrest and stabilize while melanomas grow relentlessly. The difference in their long-term growth potential can in part be attributed to activation of cellular senescence pathways. The primary mediator of senescence in nevi appears to be p16. Redundant, secondary senescence systems are also present and include the p14-p53-p21 pathway, the IGFBP7 pathway, the FBXO31 pathway, and the PI3K-mediated stress-induced endoplasmic reticulum unfolded protein response. It is evident that these senescence pathways result in an irreversible arrest in most instances; however, they can clearly be overcome in melanoma. Circumvention of these pathways is most frequently associated with gene deletion or transcriptional repression. Reactivation of senescence mechanisms could serve to inhibit melanoma tumor progression.

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Conflict of Interest

DigitalDerm, Inc – major shareholder. Spectral Image, Inc – past grants and consulting. MELA Sciences – past grants and consulting. Genentech – ­consultant. Archives of Dermatology, skINsight – section editor.

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Authors and Affiliations

  1. Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Room 912, BRB 1501 NW 10th Ave, Miami, FL, 33136, USA

    Andrew L. Ross, Margaret I. Sanchez & James M. Grichnik M.D., Ph.D.

  2. Melanoma Program, Department of Dermatology and Cutaneous Surgery, Sylvester Comprehensive Cancer Center, Miami, FL, USA

    James M. Grichnik M.D., Ph.D.

  3. Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, USA

    James M. Grichnik M.D., Ph.D.

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  1. Andrew L. Ross
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  2. Margaret I. Sanchez
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  3. James M. Grichnik M.D., Ph.D.
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Correspondence to James M. Grichnik M.D., Ph.D. .

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Editors and Affiliations

  1. Skin Cancer Center, Hauppauge Dermatology Section, Memorial Sloan Kettering, Veterans Memorial Highway 800, Hauppauge, 11788, New York, USA

    Ashfaq A. Marghoob

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Ross, A.L., Sanchez, M.I., Grichnik, J.M. (2012). Nevus Senescence: An Update. In: Marghoob, A. (eds) Nevogenesis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28397-0_10

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