TAF15 contributes to the radiation-inducible stress response in cancer

Abstract

Resistance to radiation therapy is a significant problem in the treatment of nonsmall 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 anticancer antibodies and enhances cell viability in response to radiation.

Liquid–liquid phase separation in tumor biology

“…TAF15 overexpression is associated with poor prognosis in patients NSCLC patients. 371 Aberrant gene transcription through loci-specific phase separation, which contribute to oncogenic transformation ability in relevant cancers. 372 P-TEFb 7SK snRNP complex, super elongation complex (SEC) Nucleus 1.…”

BVES‐AS1 inhibits the malignant behaviors of colon adenocarcinoma cells via regulating BVES

“…Dysfunction of RBPs can cause changes to the expression of cancer‐related genes, leading to aberrant biological behaviors (Helder et al, 2016). TATA‐box binding protein associated factor 15 (TAF15) is a member of the FET family and exerts an important role in affecting messenger RNA (mRNA) stability, RNA splicing, and transportation (Singh et al, 2020). In our study, the correlation between BVES‐AS1 and TAF15 in COAD was tested.…”

TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway

“…An increasing number of studies have described that TAF15 is also involved in the cellular stress response, cell spreading and cell adhesion 10 , 28 , which are well known to play a crucial role in tumour cell migration and invasion 29 . Moreover, studies have revealed that TAF15 is associated with the processes of various of malignant tumours including non-small cell lung cancer and melanoma 8 , 13 . Nevertheless, not much is known about TAF15 in GC.…”

“…FET proteins are mainly present in the cell nucleus 10 , however, they are also present in the cell surface and cytoplasm 11 , 12 . Therefore, they have an extended function, including regulation and interaction with a number of various proteins 9 , 13 – 15 . FUS (fused in sarcoma/translocated in liposarcoma, FUS/TLS), a member of the FET family, can interact with lncRNA-MIR137HG and ultimately promote GC progression 16 .…”

“…A study has reported that the human antibody PAT-BA4 recognizes a tumour-specific TAF15 antigen that inhibits tumour cell adhesion and spreading in stomach cancer and melanoma 8 . Overexpression of TAF15 is correlated with worsened survival in non-small cell lung cancer patients 13 . Additionally, TAF15 is involved in the drug tolerance of several cancer cells 24 .…”