Related Experiment Video

Updated: Jan 22, 2026

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
08:01

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Published on: April 21, 2022

2.2K

Identification of a novel EphB4 phosphodegron regulated by the autocrine IGFII/IRA axis in malignant mesothelioma

Pierluigi Scalia1,2,3, Giuseppe Pandini4, Vincenzo Carnevale5

  • 1Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, Biology Department, Temple University, Philadelphia, PA, 19122, USA. pscalia@isoprog.org.

Oncogene
|July 5, 2019
PubMed

Insights

Malignant mesothelioma cells maintain EphB4 expression through a novel IGF-II signaling pathway. This pathway involves insulin receptor-A, controlling EphB4 degradation and impacting cancer growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Malignant mesothelioma has limited treatment options.
  • EphB4 receptor tyrosine kinase is implicated in cancer progression and tumor microenvironment.
  • The molecular mechanisms driving EphB4's oncogenic role are not fully understood.

Purpose of the Study:

  • To elucidate the molecular network regulating EphB4 expression in malignant mesothelioma.
  • To investigate the role of Insulin-like Growth Factor II (IGF-II) in controlling EphB4 levels.
  • To identify novel therapeutic targets for malignant mesothelioma and IGF-II-secreting tumors.

Main Methods:

  • Analysis of EphB4 expression in malignant mesothelioma cells upon IGF-II neutralization.
  • Investigation of the autocrine IGF-II-insulin receptor-A signaling axis.
  • Characterization of EphB4 post-translational modifications (PTMs), including phosphorylation and ubiquitination.
  • 3D modeling to visualize EphB4 regulation.

Main Results:

  • EphB4 expression decreases when cancer-secreted IGF-II is neutralized.
  • EphB4 protein levels are maintained by an IGF-II-driven signaling axis involving insulin receptor-A.
  • IGF-II stimulates insulin receptor-A to phosphorylate EphB4 at tyrosine 987, preventing its degradation.
  • Inhibition of this phosphorylation leads to EphB4 ubiquitination and rapid degradation.
  • A novel ubiquitin-binding motif within the EphB4 phosphodegron was identified.

Conclusions:

  • A novel mechanism maintains EphB4 expression in malignant mesothelioma via an autocrine IGF-II/Insulin Receptor-A pathway.
  • This pathway regulates EphB4 stability through phosphorylation-dependent degradation.
  • Findings offer potential therapeutic strategies targeting this axis in malignant mesothelioma and IGF2omas.

More Related Videos

Isolating Malignant and Non-Malignant B Cells from lck:eGFP Zebrafish08:32

Isolating Malignant and Non-Malignant B Cells from lck:eGFP Zebrafish

Published on: February 22, 2019

7.5K
Identification of Novel Regulators of Plant Transpiration by Large-Scale Thermal Imaging Screening in Helianthus Annuus07:08

Identification of Novel Regulators of Plant Transpiration by Large-Scale Thermal Imaging Screening in Helianthus Annuus

Published on: January 30, 2020

6.4K

Related Concept Videos

Autocrine Signaling01:01

Autocrine Signaling

Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
Autocrine Signaling in Macrophages
Under normal physiological conditions, autocrine signaling is essential for maintaining homeostasis. This process is well characterized in...
52.1K
Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
65.7K
Perpendicular-Axis Theorem01:16

Perpendicular-Axis Theorem

The perpendicular-axis theorem states that the moment of inertia of a planar object about an axis perpendicular to its plane is equal to the sum of the moments of inertia about two mutually perpendicular concurrent axes lying in the plane of the body.
Consider a circular disc of mass M and radius R lying along an x-y plane. The origin lies at the center of the disc, and the z-axis is perpendicular to the disc's plane. All three axes coincide at the disc's center. The moment of inertia of this...
4.5K
Parallel-axis Theorem01:06

Parallel-axis Theorem

The parallel-axis theorem provides a convenient and quick method of finding the moment of inertia of an object about an axis parallel to the axis passing through its center of mass. Consider a thin rod as an example. There is a striking similarity between the process of finding the moment of inertia of a thin rod about an axis through its middle, where the center of mass lies, and about an axis through its end using the conventional method. In the conventional method, the concept of linear mass...
8.2K
Moment of Inertia about an Arbitrary Axis01:20

Moment of Inertia about an Arbitrary Axis

The moment of inertia is typically associated with principal axes, but it can also be computed for any random axis. When an arbitrary axis is under consideration, the moment of inertia is determined by integrating the mass distribution of the object along that specific axis. It is crucial in applications like the design of machinery, where components rotate about various axes, and balance and stability are essential.
In this scenario, the perpendicular distance between the chosen arbitrary axis...
619
Angular Momentum about an Arbitrary Axis01:11

Angular Momentum about an Arbitrary Axis

Imagine a rigid body with a mass denoted as 'm', which has its center of mass at point G and is rotating around an inertial reference frame. The angular momentum at an arbitrary point P can be calculated by taking the cross product of the position vector and linear momentum vector for each individual mass element.
The velocity of a mass element comprises its translational velocity and the relative velocity instigated by the body's rotation. Substituting the velocity equation into...
444