• Tumors change their metabolism to spread

    From ScienceDaily@1:317/3 to All on Wednesday, April 13, 2022 22:30:44
    Tumors change their metabolism to spread more effectively

    Date:
    April 13, 2022
    Source:
    Weill Cornell Medicine
    Summary:
    Cancer cells can disrupt a metabolic pathway that breaks down fats
    and proteins to boost the levels of a byproduct called methylmalonic
    acid, thereby driving metastasis, according to new research. The
    findings open a new lead for understanding how tumors metastasize,
    or spread to other tissues, and hints at novel ways to block the
    spread of cancer by targeting the process.



    FULL STORY ========================================================================== Cancer cells can disrupt a metabolic pathway that breaks down fats and
    proteins to boost the levels of a byproduct called methylmalonic acid,
    thereby driving metastasis, according to research led by scientists at
    Weill Cornell Medicine.

    The findings open a new lead for understanding how tumors metastasize,
    or spread to other tissues, and hints at novel ways to block the spread
    of cancer by targeting the process.


    ==========================================================================
    The new results, published March 31 in Nature Metabolism, show that
    metastatic tumors suppress the activity of a key enzyme in propionate metabolism, the process by which cells digest certain fatty acids and
    protein components.

    Suppressing the enzyme increases production of methylmalonic acid
    (MMA). That, in turn, causes the cells to become more aggressive and
    invasive.

    Cancer is the second leading cause of death worldwide, and metastasis
    drives much of that mortality. Once a tumor begins to metastasize to
    different tissues and organs around the body, it can quickly become
    difficult or impossible to treat. However, researchers have made few
    inroads in understanding how a tumor cell acquires the ability to
    metastasize.

    "A lot of work has been focused on primary tumor initiation and growth,
    or examining the metastatic tumor, but to go from the primary tumor to the metastatic tumor, that transition has not been studied very extensively,"
    said co-senior author Dr. John Blenis, the Anna-Maria and Stephen Kellen Professor in Cancer Research, professor of pharmacology and associate
    director of basic science of the Sandra and Edward Meyer Cancer Center
    at Weill Cornell Medicine.

    To address that gap, Dr. Blenis and his colleagues have worked for several years to characterize the metabolic changes that cells undergo during the metastatic transition. That effort previously revealed that as people age, their bodies produce more serum MMA (although the source remains unknown),
    and that higher MMA levels drive worse cancer outcomes. Healthy cells
    also produce MMA, though, so in the new study Dr. Blenis's team probed
    the metabolite's cancer-related activities more deeply.

    "Cancer cells themselves can hijack the pathway that makes methylmalonic
    acid and this forms a feed-forward cycle that drives cancer progression
    towards more aggressive and more metastatic forms," said co-first
    author Dr. Vivien Low, a postdoctoral fellow in Dr. Blenis's lab. The
    other co-first authors Dr. Ana Gomes and Dr. Didem Ilter, were also postdoctoral fellows in the lab at the time of the study. Dr. Gomes is
    now a faculty member and Dr. Ilter is a research scientist at H. Lee
    Moffitt Cancer Center & Research Institute.

    The discovery adds to a growing body of work showing that specific
    products of metabolism, called oncometabolites, can drive many aspects
    of cancer progression and metastasis.

    While the new paper focused on various models of breast cancer, Dr. Low
    said the team is now analyzing other types of cancer cells as well,
    where they expect to find similar mechanisms operating. The scientists
    are also searching for ways to attack the process.

    "Metastasis is responsible for about 80 to 90 percent of cancer-related mortality, so if we can predict when someone has the potential to
    develop metastatic tumors, or treat those metastatic tumors that might
    have this pathway up-regulated, then we might have a very effective,
    novel therapy," Dr.

    Blenis said.


    ========================================================================== Story Source: Materials provided by Weill_Cornell_Medicine. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Ana P. Gomes, Didem Ilter, Vivien Low, Stanislav Drapela, Tanya
    Schild,
    Edouard Mullarky, Julie Han, Ilaria Elia, Dorien Broekaert, Adam
    Rosenzweig, Michal Nagiec, Joana B. Nunes, Bethany E. Schaffer,
    Anders P.

    Mutvei, John M. Asara, Lewis C. Cantley, Sarah-Maria Fendt,
    John Blenis.

    Altered propionate metabolism contributes to tumour
    progression and aggressiveness. Nature Metabolism, 2022; DOI:
    10.1038/s42255-022-00553-5 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220413131215.htm

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