Related Experiment Video

Updated: Jan 28, 2026

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract
09:41

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Published on: June 17, 2014

12.5K

Tegavivint and the β-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma

Motonari Nomura, Nino Rainusso, Yi-Chien Lee

    Journal of the National Cancer Institute
    |February 23, 2019
    PubMed
    Abstract

    Insights

    Tegavivint effectively inhibits osteosarcoma (OS) growth and metastasis by targeting the β-catenin/ALDH1 pathway. This novel inhibitor shows promise for treating advanced OS, though bone density reduction was observed in male mice.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Pharmacology

    Background:

    • The Wnt/β-catenin pathway is implicated in osteosarcoma (OS) development and metastasis.
    • Targeting this pathway presents a therapeutic opportunity for OS treatment.

    Purpose of the Study:

    • To investigate the antitumor activity of Tegavivint, a novel β-catenin/transducin β-like protein 1 (TBL1) inhibitor, against osteosarcoma.
    • To evaluate Tegavivint's efficacy in preclinical models of high-risk OS.

    Main Methods:

    • In vitro and ex vivo studies using OS and patient-derived xenograft (PDX) cell lines.
    • In vivo evaluation in chemoresistant and metastatic OS PDX models.
    • Assessment of β-catenin and aldehyde dehydrogenase 1 (ALDH1) expression and activity.

    Main Results:

    • Tegavivint demonstrated antiproliferative effects on OS cells and reduced pulmonary metastasis in vitro and ex vivo.
    • Tegavivint suppressed tumor growth in OS PDX models, including chemoresistant and metastatic variants.
    • Tegavivint decreased β-catenin and ALDH1 expression and activity in metastatic OS cells, with ALDH1high cells showing sensitivity.

    Conclusions:

    • Tegavivint exhibits significant antitumor activity against osteosarcoma by targeting the β-catenin/ALDH1 axis.
    • Tegavivint is a potential therapeutic agent for advanced osteosarcoma.
    • Further investigation into Tegavivint's toxicity, including bone density effects, is warranted.

    More Related Videos

    Practical Considerations in Studying Metastatic Lung Colonization in Osteosarcoma Using the Pulmonary Metastasis Assay07:44

    Practical Considerations in Studying Metastatic Lung Colonization in Osteosarcoma Using the Pulmonary Metastasis Assay

    Published on: March 12, 2018

    10.6K
    Modeling Chemotherapy Resistant Leukemia In Vitro08:41

    Modeling Chemotherapy Resistant Leukemia In Vitro

    Published on: February 9, 2016

    9.5K

    Related Concept Videos

    Catenins01:23

    Catenins

    Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
    Catenins in Cell Junctions
    Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
    3.1K
    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.
    65.9K
    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...
    4.6K
    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...
    8.3K
    Load along a Single Axis01:29

    Load along a Single Axis

    In structural engineering, the analysis of beams subjected to varying loads is a critical aspect of understanding the behavior and performance of these structural elements. A common scenario involves a beam subjected to a combination of different load distributions.
    Consider a beam of length L subjected to a varying load, which is a combination of parabolic and trapezoidal load distribution along the x-axis. In this case, it is essential to determine the resultant loads, their locations, and...
    643
    Parallel-Axis Theorem for an Area01:12

    Parallel-Axis Theorem for an Area

    The moment of inertia is a fundamental concept in mechanical engineering that plays a significant role in designing rotationally symmetric objects such as flywheels, gears, and other mechanical systems. In this context, we will discuss the moment of inertia of a flywheel rotating about its centroidal axis and how it relates to the moment of inertia about an axis parallel to it.
    For a flywheel approximated as a solid disc, consider an infinitesimal differential element with an arbitrary distance...
    3.0K