Related Experiment Video

Updated: Jan 28, 2026

Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation
11:24

Measuring DNA Damage and Repair in Mouse Splenocytes After Chronic In Vivo Exposure to Very Low Doses of Beta- and Gamma-Radiation

Published on: July 3, 2015

11.5K

Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA

Jianhui Ma1, Jorge A Benitez1, Jie Li2

  • 1Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.

Cancer Cell
|March 5, 2019
PubMed

Insights

Glioblastoma treatment resistance to radiation therapy involves PTEN phosphorylation. Blocking this mechanism enhances tumor sensitivity to radiation, improving survival in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Standard glioblastoma treatments like ionizing radiation (IR) and chemotherapy are limited by therapeutic resistance.
  • DNA damage is a hallmark of these treatments, but resistance mechanisms hinder clinical efficacy.

Purpose of the Study:

  • To identify the molecular mechanisms underlying therapeutic resistance in glioblastoma.
  • To investigate the role of PTEN phosphorylation in radiation resistance.
  • To explore FGFR2 as a potential therapeutic target.

Main Methods:

  • Investigated the phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) mediated by FGFR2.
  • Assessed the binding of pY240-PTEN to chromatin via Ki-67 interaction post-IR.
  • Evaluated the recruitment of RAD51 to DNA damage sites.
  • Utilized Y240F-Pten knockin mice and GBM preclinical models to test therapeutic interventions.

Main Results:

  • Identified FGFR2-mediated phosphorylation of PTEN at tyrosine 240 (pY240-PTEN) as a key mechanism of IR resistance.
  • Demonstrated that pY240-PTEN rapidly elevates and binds to chromatin with Ki-67 in response to IR, promoting DNA repair via RAD51 recruitment.
  • Showed that blocking Y240 phosphorylation confers radiation sensitivity and extends survival in GBM preclinical models.
  • Confirmed radiation sensitivity in Y240F-Pten knockin mice.

Conclusions:

  • FGFR-mediated pY240-PTEN is a critical driver of radiation resistance in glioblastoma.
  • Targeting FGFR-mediated pY240-PTEN represents a promising strategy to enhance radiotherapy efficacy.
  • Inhibition of this pathway offers a potential therapeutic avenue for improving patient survival.
Keywords:
DNA damageFGFR2GBMPTENionizing radiation (IR)tyrosine phosphorylation

More Related Videos

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells05:18

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

11.8K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

11.0K

Related Concept Videos

Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
33.6K
Overview of DNA Repair02:25

Overview of DNA Repair

9.8K
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
53.8K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
8.0K
Biological Effects of Radiation02:59

Biological Effects of Radiation

All radioactive nuclides emit high-energy particles or electromagnetic waves. When this radiation encounters living cells, it can cause heating, break chemical bonds, or ionize molecules. The most serious biological damage results when these radioactive emissions fragment or ionize molecules. For example, α and β particles emitted from nuclear decay reactions possess much higher energies than ordinary chemical bond energies. When these particles strike and penetrate matter, they...
17.8K
Nuclear Overhauser Enhancement (NOE)01:06

Nuclear Overhauser Enhancement (NOE)

Irradiation of a spin-active nucleus causes an increase or decrease in the signal intensity of neighboring nuclei that are not necessarily chemically bonded or involved in J-coupling. This phenomenon, called the nuclear Overhauser enhancement (NOE), results from through-space interactions between the nuclear spins. The NOE effect decreases with increasing internuclear distance and is generally not observed beyond 4 angstroms. In NOE, dipole-dipole interactions between neighboring spin-active...
1.4K