Related Experiment Video

Updated: Jun 11, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.0K

Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma

Erdong Wei1,2, Ana Mitanoska1,2, Quinn O'Brien1,2

  • 1Department of Pediatrics, University of Minnesota, 2231 6th St. SE, Minneapolis, MN 55455, USA.

Molecular Cancer
|October 4, 2024
PubMed

Insights

Targeting the EWS::FLI1 oncoprotein in Ewing sarcoma (ES) with P300/CBP inhibitors induces cancer cell senescence. This senescent state, combined with PI3K pathway senolytics, offers a promising new therapeutic strategy for ES patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Ewing sarcoma (ES) is a challenging bone and soft tissue cancer.
  • The primary therapeutic obstacle is targeting the EWS::FLI1 oncoprotein.
  • Developing effective treatments for ES remains a critical unmet need.

Purpose of the Study:

  • To investigate the effects of pharmacologically inhibiting the EWS::FLI1 transcriptional complex.
  • To identify novel therapeutic strategies for targeting ES.
  • To explore the role of P300/CBP inhibition in ES treatment.

Main Methods:

  • Pharmacological inhibition of P300/CBP in ES cells.
  • Analysis of global transcriptional outcomes.
  • Investigation of LMNB1 regulation by EWS::FLI1.
  • Induction of cellular senescence.
  • Combination therapy with senolytics targeting the PI3K pathway.

Main Results:

  • P300/CBP inhibition mimics direct EWS::FLI1 knockdown, affecting global transcription.
  • EWS::FLI1 upregulates LMNB1 through GGAA motifs and acetylation.
  • P300 inhibition reverses LMNB1 upregulation, inducing ES cell senescence.
  • Senescent ES cells are eliminated by PI3K pathway senolytics.

Conclusions:

  • Targeting P300/CBP is a viable strategy to inhibit EWS::FLI1 activity.
  • The combination of P300 inhibition and PI3K senolytics presents a synergistic therapeutic approach for ES.
  • This strategy offers a promising avenue for future clinical exploration in Ewing sarcoma treatment.
Keywords:
EWS::FLI1Ewing sarcomaLamin B1P300/CBPPharmacological targetingSenescenceSenolytics

More Related Videos

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

2.7K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.8K

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...
4.5K
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...
6.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.5K