Cell cycle- and cancer-associated gene networks activated by Dsg2: evidence of cystatin A deregulation and a potential role in cell-cell adhesion

PloS One
Abhilasha GuptaMy G Mahoney

Abstract

Cell-cell adhesion is paramount in providing and maintaining multicellular structure and signal transmission between cells. In the skin, disruption to desmosomal regulated intercellular connectivity may lead to disorders of keratinization and hyperproliferative disease including cancer. Recently we showed transgenic mice overexpressing desmoglein 2 (Dsg2) in the epidermis develop hyperplasia. Following microarray and gene network analysis, we demonstrate that Dsg2 caused a profound change in the transcriptome of keratinocytes in vivo and altered a number of genes important in epithelial dysplasia including: calcium-binding proteins (S100A8 and S100A9), members of the cyclin protein family, and the cysteine protease inhibitor cystatin A (CSTA). CSTA is deregulated in several skin cancers, including squamous cell carcinomas (SCC) and loss of function mutations lead to recessive skin fragility disorders. The microarray results were confirmed by qPCR, immunoblotting, and immunohistochemistry. CSTA was detected at high level throughout the newborn mouse epidermis but dramatically decreased with development and was detected predominantly in the differentiated layers. In human keratinocytes, knockdown of Dsg2 by siRNA or shRNA reduced...Continue Reading

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Citations

Mar 15, 2016·Scientific Reports·Haiying LiuYong Zhao
Oct 23, 2016·Oncotarget·Andrew M OvermillerMỹ G Mahoney
Apr 18, 2020·International Journal of Genomics·Menghuang ZhaoXueqiong Zhu

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Datasets Mentioned

BETA
GSE62814
AJ251685

Methods Mentioned

BETA
transgenic
in vitro transcription
PCR
transfection
biopsies

Software Mentioned

Quant Array
Ingenuity Pathway Analysis ( IPA
GeneSpring
ImageJ

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