Related Experiment Video

Updated: Feb 15, 2026

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test
08:07

Traditional Trail Making Test Modified into Brand-new Assessment Tools: Digital and Walking Trail Making Test

Published on: November 23, 2019

11.9K

Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells

Krishna Kalyan Kolluri1, Constantine Alifrangis2, Neelam Kumar1

  • 1Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom.

Elife
|January 19, 2018
PubMed

Insights

Malignant mesothelioma (MM) is a fatal cancer. Researchers found that MM with BRCA associated protein-1 (BAP1) loss-of-function mutations are sensitive to TRAIL therapy, offering a new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • Malignant mesothelioma (MM) exhibits poor response to chemotherapy.
  • Identifying biomarkers for targeted therapies is crucial for improving MM patient outcomes.

Purpose of the Study:

  • To screen drugs for efficacy against MM cell lines.
  • To identify a molecular subset of MM sensitive to specific therapies.
  • To investigate the role of BAP1 in drug sensitivity.

Main Methods:

  • Exome sequencing of 15 MM cell lines.
  • Drug screening of 94 compounds.
  • Assessing sensitivity to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).
  • Investigating BAP1 function and its complex with ASXL1 (PR-DUB).

Main Results:

  • A subset of MM lines with BAP1 loss-of-function mutations showed heightened sensitivity to TRAIL.
  • This sensitivity was validated in human MM cultures, mouse xenografts, and tumor explants.
  • BAP1 deubiquitinase activity, via the PR-DUB complex, influences TRAIL sensitivity through transcriptional modulation.

Conclusions:

  • Loss-of-function mutations in BAP1 are a potential biomarker for predicting TRAIL sensitivity in MM.
  • Targeting BAP1-deficient MM with TRAIL agonists offers a promising therapeutic strategy.
  • Genomic stratification using BAP1 status can guide personalized treatment for malignant mesothelioma.
Keywords:
BAP1PR-DUBTRAILcancer biologyhumanhuman biologymedicinemesotheliomamouse

More Related Videos

A Sensitive Method to Quantify Senescent Cancer Cells09:18

A Sensitive Method to Quantify Senescent Cancer Cells

Published on: August 2, 2013

21.3K
Author Spotlight: Advancements in Hypoxia-Sensitive CAR-T Therapy for Enhanced Cancer Immunotherapy09:12

Author Spotlight: Advancements in Hypoxia-Sensitive CAR-T Therapy for Enhanced Cancer Immunotherapy

Published on: June 14, 2024

1.4K

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.1K
Line Loss01:10

Line Loss

The different configurations of source-load connections include wye (star) and delta connections. The relationship between line and phase voltages and currents varies depending on the configuration. When the source is supplying power, it is transmitted through the wires to the load, and during this transmission, some power is absorbed by the wires, leading to line loss.
Line loss impacts power delivery efficiency in a balanced three-phase circuit. The symmetry in such a circuit simplifies the...
550
Reducing Line Loss01:18

Reducing Line Loss

In a three-phase circuit, line loss is an indicator of energy dissipated as heat due to the resistance of transmission lines. To address this, incorporating transformers into the system—a step-up transformer at the source and a step-down transformer at the load—is a strategic solution. Two three-phase transformers are introduced to improve this.
With a step-up transformer at the source, the voltage is increased, thereby reducing the current in the transmission lines since power loss in...
396
Major Losses in Pipes01:28

Major Losses in Pipes

When a fluid flows through a pipe, it experiences energy losses due to frictional resistance along the pipe walls, known as major losses. These energy losses result in a pressure drop, which varies based on the flow conditions — whether laminar or turbulent — and the specific physical properties of the fluid and pipe.
Fluid flow can be classified as laminar or turbulent, primarily based on the Reynolds number. This dimensionless number reflects the relative influence of inertial to viscous...
2.0K
Minor Losses in Pipes01:25

Minor Losses in Pipes

In pipe systems, minor losses refer to energy losses arising from components such as valves, bends, fittings, expansions, and other features that disrupt the steady flow of fluid. These disturbances cause energy dissipation through turbulence and resistance, which engineers quantify to manage system efficiency effectively.
Valves play a significant role in generating minor losses by obstructing or redirecting the fluid flow. When a valve is closed or partially closed, it restricts the flow...
2.0K
Energy Losses in Transformers01:21

Energy Losses in Transformers

In an ideal transformer, it is assumed that there are no energy losses, and, hence, all the power at the primary winding is transferred to the secondary winding. However, in reality,  the transformers always have some energy losses, and, hence, the output power obtained at the secondary winding is less than the input power at the primary winding due to energy losses.
There are four main reasons for energy losses in transformers.
The first cause can be  the high resistance of the...
1.4K