Oncotarget

Research Papers:

EGR1 interacts with TBX2 and functions as a tumor suppressor in rhabdomyosarcoma

Trefa Mohamad, Noor Kazim, Abhinav Adhikari and Judith K. Davie _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2018; 9:18084-18098. https://doi.org/10.18632/oncotarget.24726

Metrics: PDF 2463 views  |   HTML 4822 views  |   ?  


Abstract

Trefa Mohamad1, Noor Kazim1, Abhinav Adhikari1 and Judith K. Davie1

1Department of Biochemistry and Molecular Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA

Correspondence to:

Judith K. Davie, email: [email protected]

Keywords: EGR1; TBX2; RMS; apoptosis

Received: February 15, 2018     Accepted: February 21, 2018     Published: April 06, 2018

ABSTRACT

EGR1, one of the immediate-early response genes, can function as a tumor suppressor gene or as an oncogene in cancer. The function of EGR1 has not been fully characterized in rhabdomyosarcoma (RMS), a pediatric cancer derived from the muscle linage. We found that EGR1 is downregulated in the alveolar RMS (ARMS) subtype but expressed at levels comparable to normal skeletal muscle in embryonal RMS (ERMS). We found that overexpression of EGR1 in ARMS significantly decreased cell proliferation, mobility, and anchorage-independent growth while also promoting differentiation. We found that EGR1 interacts with TBX2, which we have shown functions as an oncogene in RMS. The interaction inhibits EGR1 dependent gene expression, which includes the cell cycle regulators p21 and PTEN as well as other important cell growth drivers such as NDRG1 and CST6. We also found that EGR1 induced apoptosis by triggering the intrinsic apoptosis pathway. EGR1 also activated two pro-apoptotic factors, BAX and dephosphorylated BAD, which are both located upstream of the caspase cascades in the intrinsic pathway. EGR1 also sensitized RMS cells to chemotherapeutic agents, suggesting that activating EGR1 may improve therapeutic targeting by inducing apoptosis. Our results establish the important role of EGR1 in understanding RMS pathology.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24726