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Comment
. 2018 Jul 9;34(1):1-3.
doi: 10.1016/j.ccell.2018.06.010.

BRN 2 Invade

Gaurav Pathria  1 , Ze'ev A Ronai  2
Affiliations
Comment

BRN 2 Invade

Gaurav Pathria et al. Cancer Cell. .

Abstract

One of the remaining challenges in treating melanoma is its strong propensity to metastasize. Thus, there is considerable interest in understanding the alterations that drive progression of the disease. In this issue of Cancer Cell, Shain et al. and Zheng et al. provide insights implicating p16INK4A in melanoma invasiveness.

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Figures

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Loss of CDKN2A Induces BRN2-Mediated Melanoma Invasion
In non-malignant melanocytic nevi/melanoma in situ, the CDK4/CDK6 inhibitor p16INK4A is transcribed from the CDKN2A gene and maintains the activity of the tumor suppressor Rb, which binds to and blocks the function of the transcription factor E2F1. Because E2F1 is a transcriptional modulator of BRN2, the presence of a functional CDKN2A gene and normal p16INK4A levels successfully controls BRN2 expression. However, widespread loss of the CDKN2A locus as precursor lesions transition to the malignant state prevents the p16INK4A-mediated block in BRN2 expression, which promotes invasion.
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References

    1. Fane ME, Chhabra Y, Smith AG, and Sturm RA (2018). BRN2, a POUerful driver of melanoma phenotype switching and metastasis. Pigment Cell Melanoma Res. - PubMed
    1. Goodall J, Carreira S, Denat L, Kobi D, Davidson I, Nuciforo P, Sturm RA, Larue L, and Goding CR (2008). Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells. Cancer Res 68, 7788–7794. - PubMed
    1. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, et al. (2012). A landscape of driver mutations in melanoma. Cell 150, 251–263. - PMC - PubMed
    1. Li J, Poi MJ, and Tsai MD (2011). Regulatory mechanisms of tumor suppressor P16(INK4A) and their relevance to cancer. Biochemistry 50, 5566–5582. - PMC - PubMed
    1. Otto T, and Sicinski P (2017). Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer 17, 93–115. - PMC - PubMed

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