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Hmga2 translocation induced in skin tumorigenesis

Hmga2 protein, a transcription factor involved in chromatin architecture, is expressed chiefly during development, where it has many key biological functions. When expressed in adult tissues from in various organs, Hmga2 is always related to cancer development. The role of Hmga2 in skin tumorigenesi...

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Autores principales: Li, Yong, Pi, Xiang-ying, Boland, Kelsey, Lad, Sonali, Johnson, Kelly, Verfaillie, Catherine, Morris, Rebecca J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444722/
https://www.ncbi.nlm.nih.gov/pubmed/28415789
http://dx.doi.org/10.18632/oncotarget.16272
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author Li, Yong
Pi, Xiang-ying
Boland, Kelsey
Lad, Sonali
Johnson, Kelly
Verfaillie, Catherine
Morris, Rebecca J.
author_facet Li, Yong
Pi, Xiang-ying
Boland, Kelsey
Lad, Sonali
Johnson, Kelly
Verfaillie, Catherine
Morris, Rebecca J.
author_sort Li, Yong
collection PubMed
description Hmga2 protein, a transcription factor involved in chromatin architecture, is expressed chiefly during development, where it has many key biological functions. When expressed in adult tissues from in various organs, Hmga2 is always related to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not yet understood. We demonstrated that Hmga2 can be found in non-transformed epidermis, specifically located to the membrane of keratinocytes (KCs) in epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and TPA mouse models was associated with translocation of the Hmga2 protein from the membrane into the nucleus, where Hmga2 induced its own expression by binding to the Hmga2 promoter. Panobinostat, an HDAC inhibitor, downregulated Hmga2 expression by preventing Hmga2 to bind its own promoter, and thus inhibiting Hmga2 promoter activity. Hmga2 translocation to the nucleus could in part be prevented by an inhibitor for ROCK1. Our findings demonstrate that upon program of benign papilloma to malignant cSCC of skin tumorigenesis, Hmga2 translocates in a ROCK-dependent manner from the membrane to the nucleus, where it serves as an autoregulatory transcription factor, causing cell transformation.
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spelling pubmed-54447222017-06-01 Hmga2 translocation induced in skin tumorigenesis Li, Yong Pi, Xiang-ying Boland, Kelsey Lad, Sonali Johnson, Kelly Verfaillie, Catherine Morris, Rebecca J. Oncotarget Research Paper Hmga2 protein, a transcription factor involved in chromatin architecture, is expressed chiefly during development, where it has many key biological functions. When expressed in adult tissues from in various organs, Hmga2 is always related to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not yet understood. We demonstrated that Hmga2 can be found in non-transformed epidermis, specifically located to the membrane of keratinocytes (KCs) in epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and TPA mouse models was associated with translocation of the Hmga2 protein from the membrane into the nucleus, where Hmga2 induced its own expression by binding to the Hmga2 promoter. Panobinostat, an HDAC inhibitor, downregulated Hmga2 expression by preventing Hmga2 to bind its own promoter, and thus inhibiting Hmga2 promoter activity. Hmga2 translocation to the nucleus could in part be prevented by an inhibitor for ROCK1. Our findings demonstrate that upon program of benign papilloma to malignant cSCC of skin tumorigenesis, Hmga2 translocates in a ROCK-dependent manner from the membrane to the nucleus, where it serves as an autoregulatory transcription factor, causing cell transformation. Impact Journals LLC 2017-03-16 /pmc/articles/PMC5444722/ /pubmed/28415789 http://dx.doi.org/10.18632/oncotarget.16272 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Li, Yong
Pi, Xiang-ying
Boland, Kelsey
Lad, Sonali
Johnson, Kelly
Verfaillie, Catherine
Morris, Rebecca J.
Hmga2 translocation induced in skin tumorigenesis
title Hmga2 translocation induced in skin tumorigenesis
title_full Hmga2 translocation induced in skin tumorigenesis
title_fullStr Hmga2 translocation induced in skin tumorigenesis
title_full_unstemmed Hmga2 translocation induced in skin tumorigenesis
title_short Hmga2 translocation induced in skin tumorigenesis
title_sort hmga2 translocation induced in skin tumorigenesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444722/
https://www.ncbi.nlm.nih.gov/pubmed/28415789
http://dx.doi.org/10.18632/oncotarget.16272
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