Oncotarget

Research Papers:

Hmga2 translocation induced in skin tumorigenesis

Yong Li _, Xiang-ying Pi, Kelsey Boland, Sonali Lad, Kelly Johnson, Catherine Verfaillie and Rebecca J. Morris

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Oncotarget. 2017; 8:30019-30029. https://doi.org/10.18632/oncotarget.16272

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Abstract

Yong Li1, Xiang-ying Pi1, Kelsey Boland1, Sonali Lad1, Kelly Johnson1, Catherine Verfaillie2, Rebecca J. Morris1

1The Hormel Institute University of Minnesota, Austin, MN 55912, United States

2Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium

Correspondence to:

Yong Li, email: Lixx2752@umn.edu

Rebecca J. Morris, email: rmorris@hi.umn.edu

Keywords: Hmga2, keratinocytes, panobinostat, ROCK, skin tumorigenesis

Received: December 16, 2016     Accepted: March 06, 2017     Published: March 16, 2017

ABSTRACT

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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