TAF15 contributes to the radiation-inducible stress response in cancer.

Oncotarget
Abhay Kumar SinghDennis E Hallahan

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.

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Methods Mentioned

BETA
RNA-Seq
flow cytometry
xenografts
co-immunoprecipitation
X-ray
FACS
immunoprecipitation

Software Mentioned

Ingenuity Pathway Analysis
Origene
Scaffold Proteome Viewer
Prism
ImageJ
GraphPad
Graph Pad Prism
Gene Expression Profiling Interactive Analysis ( GEPIA )
Ingenuity Pathway Analysis ( IPA )
FlowJo

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