Related Experiment Video

Updated: Apr 14, 2026

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
09:37

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

Published on: August 25, 2021

2.3K

Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis

Yan Xiang, Zachary E Stine, Jinsong Xia

    The Journal of Clinical Investigation
    |April 28, 2015
    PubMed

    Insights

    Glutaminase (GLS) is crucial for cancer growth. Inhibiting GLS blocks tumor progression and DNA replication, offering a potential cancer therapy targeting tumor cell metabolism.

    Area of Science:

    • Oncology
    • Cancer Metabolism
    • Biochemistry

    Background:

    • Glutaminase (GLS) facilitates glutamine to glutamate conversion, vital for cancer cell metabolism, growth, and proliferation.
    • The therapeutic potential of GLS inhibitors is under investigation, but their specific effects on tumor-autonomous growth, the microenvironment, and off-target impacts remain unclear.

    Purpose of the Study:

    • To investigate the role of GLS in cancer progression and evaluate GLS inhibitors as a therapeutic strategy.
    • To determine if GLS inhibition affects tumor-autonomous growth or has off-target effects.

    Main Methods:

    • Utilized a MYC-mediated hepatocellular carcinoma mouse model and a MYC-dependent human B cell lymphoma cell line (P493).
    • Administered the GLS-specific inhibitor BPTES and employed Vivo-Morpholinos targeting human and mouse GLS mRNA.
    • Assessed tumor progression, survival rates, DNA replication, cell death, and GLS expression in response to treatments.

    Main Results:

    • Loss of one Gls copy blunted tumor progression in a mouse model of hepatocellular carcinoma.
    • BPTES treatment prolonged survival in mice with MYC-induced hepatocellular carcinoma and inhibited P493 lymphoma cell growth by blocking DNA replication.
    • BPTES efficacy was dependent on GLS activity, as evidenced by resistance in GLS mutant or overexpressing xenografts, and targeted inhibition of human GLS mRNA reduced xenograft growth without affecting mouse Gls.

    Conclusions:

    • GLS is essential for tumorigenesis, demonstrating a tumor cell-autonomous dependence.
    • Targeting GLS through small molecule inhibitors or genetic approaches represents a promising strategy for cancer therapy.

    More Related Videos

    Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases14:57

    Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

    Published on: October 10, 2020

    15.4K
    Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care12:55

    Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

    Published on: February 16, 2015

    22.2K

    Related Concept Videos

    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...
    9.2K
    Tumor Immunotherapy01:27

    Tumor Immunotherapy

    Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
    2.5K
    Combination Therapies and Personalized Medicine02:50

    Combination Therapies and Personalized Medicine

    Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
    The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
    6.4K