TAF15 contributes to the radiation-inducible stress response in cancer

Abhay Kumar Singh1, Vaishali Kapoor1, Dinesh Thotala1,2

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

Oncotarget
|July 18, 2020
PubMed

Insights

TAF15 is a radiation-inducible protein that worsens survival in non-small cell lung cancer (NSCLC). Silencing TAF15 or targeting it with an antibody enhances radiation therapy effectiveness, offering new treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Radiation resistance is a major challenge in non-small cell lung cancer (NSCLC) treatment.
  • Novel molecular targets are needed for combination therapies.
  • TAF15 was identified as a radiation-inducible protein.

Purpose of the Study:

  • To investigate the role of TAF15 in NSCLC radiation resistance.
  • To evaluate TAF15 as a therapeutic target for NSCLC.

Main Methods:

  • Phage-displayed peptide libraries to identify radiation-inducible targets.
  • Genetic silencing of TAF15 in NSCLC cells.
  • In vitro and in vivo studies of TAF15 expression and function.
  • Antibody-based targeting of surface-expressed TAF15.

Main Results:

  • TAF15 overexpression correlates with poorer survival in NSCLC patients.
  • Radiation induces TAF15 expression on the cell surface.
  • TAF15 depletion causes cell cycle arrest, apoptosis, and reduced proliferation.
  • Combined radiation and TAF15 knockdown significantly reduce cancer cell survival.
  • Anti-TAF15 antibody treatment combined with radiation decreases cancer cell survival.

Conclusions:

  • TAF15 is a radiation-inducible target that promotes NSCLC cell viability.
  • Surface-expressed TAF15 is accessible to antibody-based therapies.
  • Targeting TAF15 offers a promising strategy to overcome radiation resistance in NSCLC.

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