ETS-Domain Transcription Factor Elk-1 Regulates Stemness Genes in Brain Tumors and CD133+ BrainTumor-Initiating Cells

• Main Authors: Melis Savasan Sogut, Chitra Venugopal, Basak Kandemir, Ugur Dag, Sujeivan Mahendram, Sheila Singh, Gizem Gulfidan, Kazim Yalcin Arga, Bayram Yilmaz, Isil Aksan Aksan Kurnaz
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Journal of Personalized Medicine
• Subjects: ETS; Elk-1; stem cell; microarray; brain-tumor-initiating cell (BTIC)
• Online Access: https://www.mdpi.com/2075-4426/11/2/125

Elk-1, a member of the ternary complex factors (TCFs) within the ETS (E26 transformation-specific) domain superfamily, is a transcription factor implicated in neuroprotection, neurodegeneration, and brain tumor proliferation. Except for known targets, <i>c-fos</i> and <i>egr-1</i>, few targets of Elk-1 have been identified. Interestingly, <i>SMN</i>, <i>SOD1, </i>and <i>PSEN1 </i>promoters were shown to be regulated by Elk-1. On the other hand, Elk-1 was shown to regulate the CD133 gene, which is highly expressed in brain-tumor-initiating cells (BTICs) and used as a marker for separating this cancer stem cell population. In this study, we have carried out microarray analysis in SH-SY5Y cells overexpressing Elk-1-VP16, which has revealed a large number of genes significantly regulated by Elk-1 that function in nervous system development, embryonic development, pluripotency, apoptosis, survival, and proliferation. Among these, we have shown that genes related to pluripotency, such as <i>Sox2</i>, <i>Nanog</i>, and <i>Oct4</i>, were indeed regulated by Elk-1, and in the context of brain tumors, we further showed that Elk-1 overexpression in CD133+ BTIC population results in the upregulation of these genes. When Elk-1 expression is silenced, the expression of these stemness genes is decreased. We propose that Elk-1 is a transcription factor upstream of these genes, regulating the self-renewal of CD133+ BTICs.