Related Experiment Video

Updated: Aug 10, 2025

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
09:33

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

Published on: August 25, 2023

1.2K

Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic

Zaili Luo1, Dazhuan Xin1, Yunfei Liao1

  • 1Brain Tumor Center, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Nature Communications
|February 10, 2023
PubMed

Insights

Mutations in CTDNEP1 are linked to aggressive MYC-driven medulloblastomas. CTDNEP1 loss promotes tumor growth by stabilizing MYC and causing instability, suggesting CTDNEP1 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MYC-driven medulloblastomas are aggressive childhood brain tumors.
  • The molecular drivers of MYC amplification and malignant transformation are not fully understood.

Purpose of the Study:

  • Investigate the role of CTDNEP1 mutations in MYC-driven medulloblastomas.
  • Determine the functional impact of CTDNEP1 deficiency on tumor development and progression.
  • Identify potential therapeutic strategies for CTDNEP1-deficient tumors.

Main Methods:

  • Genomic analysis of medulloblastoma patient samples to identify recurrent mutations.
  • Murine models to study the functional consequences of Ctdnep1 ablation.
  • Phosphoproteomic analysis to identify CTDNEP1-regulated pathways.
  • In vivo studies to evaluate combination therapy efficacy.

Main Results:

  • Mutations in CTDNEP1 are significantly enriched in MYC-driven medulloblastomas, defining high-risk subsets.
  • Ctdnep1 ablation in mice promotes cerebellar progenitor transformation into MYC-amplified medulloblastomas.
  • CTDNEP1 deficiency stabilizes and activates MYC by increasing S62 phosphorylation, leading to chromosomal instability, p53 loss, and MYC amplification.
  • CTDNEP1 regulates key mitotic regulators, including TOP2A and CHEK1.
  • Combined targeting of MYC and CHEK1 synergistically inhibits tumor growth and improves survival in preclinical models.

Conclusions:

  • CTDNEP1 acts as a tumor suppressor in MYC-driven medulloblastomas.
  • CTDNEP1 controls MYC activity and mitotic fidelity.
  • Targeting CTDNEP1-dependent pathways represents a potential therapeutic strategy for aggressive medulloblastomas.

More Related Videos

Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice05:10

Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice

Published on: October 3, 2010

12.3K
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.9K

Related Concept Videos

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...
4.6K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.7K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.6K