Oncotarget

Research Papers:

TAF15 contributes to the radiation-inducible stress response in cancer

Abhay Kumar Singh, Vaishali Kapoor, Dinesh Thotala and Dennis E. Hallahan _

PDF  |  Full Text  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2020; 11:2647-2659. https://doi.org/10.18632/oncotarget.27663

Metrics: PDF 186 views  |   Full Text 358 views  |   ?  


Abstract

Abhay Kumar Singh1, Vaishali Kapoor1, Dinesh Thotala1,2 and Dennis E. Hallahan1,2

1 Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA

2 Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA

Correspondence to:

Dennis E. Hallahan,email: dhallahan@wustl.edu

Keywords: TAF15; radiation inducible; lung cancer; antibody

Received: February 19, 2020     Accepted: June 15, 2020     Published: July 07, 2020

ABSTRACT

Resistance to radiation therapy is a significant problem in the treatment of non-small cell lung cancer (NSCLC). There is an unmet need to discover new molecular targets for drug development in combination with standard of care cancer therapy. We found that TAF15 was radiation-inducible using phage-displayed peptide libraries. In this study, we report that overexpression of TAF15 is correlated with worsened survival in NSCLC patients. Radiation treatment led to surface induction of TAF15 in vitro and in vivo. We genetically silenced TAF15 which led to a significant reduction in proliferation of NSCLC cells. Cells depleted of TAF15 exhibited cell cycle arrest and enhanced apoptosis through activation and accumulation of p53. In combination with radiation, TAF15 knockdown led to a significant reduction in the surviving fraction of NSCLC cell lines. To determine the importance of TAF15 surface expression, we targeted TAF15 with an antibody. In combination with radiation, the anti-TAF15 antibody led to a reduction in the surviving fraction of cancer cells. These studies show that TAF15 is a radiation-inducible molecular target that is accessible to anti-cancer antibodies and enhances cell viability in response to radiation.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 27663