Related Experiment Video

Updated: Jun 4, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
10:24

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

L1CAM regulates DNA damage checkpoint response of glioblastoma stem cells through NBS1

Lin Cheng1, Qiulian Wu, Zhi Huang

  • 1Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

The EMBO Journal
|February 8, 2011
PubMed

Insights

L1CAM protein enhances brain tumor stem cell resistance to radiation therapy by regulating DNA repair. Targeting L1CAM may improve glioblastoma treatment outcomes.

Area of Science:

  • Neuro-oncology
  • Cancer Biology
  • Molecular Oncology

Background:

  • Glioblastomas (GBMs) are aggressive brain tumors with limited treatment options due to therapeutic resistance.
  • Glioblastoma stem cells (GSCs) exhibit enhanced DNA damage checkpoint activation and radioresistance, but the underlying mechanisms are unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which L1CAM influences DNA damage checkpoint responses and radiosensitivity in GSCs.
  • To investigate the role of L1CAM nuclear translocation and its downstream signaling pathways in GSC radioresistance.

Main Methods:

  • Utilized RNA interference to target L1CAM expression in GSCs.
  • Assessed DNA damage checkpoint activation, DNA repair capacity, and radiosensitivity following L1CAM manipulation.
  • Investigated the expression of NBS1 and the MRE11-RAD50-NBS1 (MRN) complex components.
  • Examined the role of L1CAM intracellular domain (L1-ICD) nuclear translocation and c-Myc in regulating NBS1 expression.

Main Results:

  • L1CAM knockdown attenuated DNA damage checkpoint activation and repair, increasing GSC radiosensitivity.
  • L1CAM regulates the expression of NBS1, a key component of the MRN complex crucial for ATM kinase activation.
  • Ectopic NBS1 expression rescued the radioresistance defects caused by L1CAM knockdown.
  • Nuclear translocation of L1-ICD mediates NBS1 upregulation via c-Myc, enhancing MRN-ATM-Chk2 signaling.

Conclusions:

  • L1CAM plays a critical role in augmenting DNA damage checkpoint activation and radioresistance in GSCs.
  • The L1CAM-L1-ICD-NBS1-c-Myc axis is a key pathway regulating GSC response to DNA damage.
  • Targeting L1CAM presents a potential therapeutic strategy to overcome radioresistance in glioblastoma.

More Related Videos

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells10:28

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting08:14

Processing of Primary Brain Tumor Tissue for Stem Cell Assays and Flow Sorting

Published on: September 25, 2012

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...