Nav: Home

Oncotarget | SLC25A32 sustains cancer cell proliferation by regulating flavin adenine nucleotide (FAD) metabolism

February 28, 2020

OncotargetVolume 11 Issue 8 reported that while it is known that cancer cells require one-carbon and FAD-dependent mitochondrial metabolism to sustain cell proliferation, the role of SLC25A32 in cancer cell growth remains unexplored.

Si RNA-mediated knock-down and CRISPR-mediated knock-out of SLC25A32 in cancer cells of different origins, resulted in the identification of cell lines sensitive and resistant to SLC25A32 inhibition.

Treatment of cells with the FAD precursor riboflavin and with GSH rescues cancer cell proliferation upon SLC25A32 down-regulation.

Dr. Sven Christian from Bayer AG, Drug Discovery, in Berlin Germany said "Altered tumor metabolism is described as a hallmark of tumor biology and is essential for the adaptation of tumor cells to their specific needs, e. g. a higher demand for energy and macromolecules."

"Altered tumor metabolism is described as a hallmark of tumor biology and is essential for the adaptation of tumor cells to their specific needs, e. g. a higher demand for energy and macromolecules."

- Dr. Sven Christian, Bayer AG, Drug Discovery

Due to the glycolytic switch of tumor cells, mitochondrial biology and especially mitochondrial oxidative phosphorylation have been considered of minor importance in cancer biology.

Although the outer mitochondrial membrane was shown to be relatively permeable, the inner mitochondrial membrane is comparatively impermeable and consequently contains several transporter proteins to overcome such a physical barrier.

The SLC25 family consists of 53 members localized at the inner mitochondrial membrane that transport a wide range of molecules involved in essential mitochondrial processes such as redox balance, the urea and citric acid cycles, oxidative phosphorylation, DNA maintenance and iron metabolism.

Uncoupling proteins are transporting protons across the mitochondrial membrane and thus, uncouple the transport from ATP generation.

In support of this, yeast lacking the mitochondrial FAD transporter FLX1, could be rescued by human SLC25A32 expression, suggesting that this transporter may also transport FAD across the inner membrane.

The Christian Research Team concluded in their Oncotarget Research Article that the data suggests that inhibition of SLC25A32 is anti-proliferative in a subset of tumor cell lines, at least partially by an increase of reactive oxygen species as a result of a malfunctional FAD-dependent enzymes such as SDH and that resistant cell line can compensate for the loss by the availability of higher reducing capacities. The study validates the role of SLC25A32 as a novel cancer target involved in the regulation of FAD-dependent mitochondrial metabolism. Molecular targeting of SLC25A32 using a single agent or in combination with ROS-inducing therapies could be an effective clinical strategy to successfully treat cancer patients.

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27486

Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=27486&path[]=89920

Correspondence to - Sven Christian - sven.christian@bayer.com

Keywords - transporter, mitochondria, metabolism, ROS, FAD

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit http://www.oncotarget.com or connect with:

SoundCloud -https://soundcloud.com/oncotarget
Facebook -https://www.facebook.com/Oncotarget/
Twitter -https://twitter.com/oncotarget
LinkedIn -https://www.linkedin.com/company/oncotarget
Pinterest -https://www.pinterest.com/oncotarget/
Reddit -https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105

Impact Journals LLC

Related Cancer Cells Articles:

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.
Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.
First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.
Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.
Plant-derived SVC112 hits cancer stem cells, leaves healthy cells alone
Study shows Colorado drug SVC112 stops production of proteins that cancer stem cells need to survive and grow.
Changes in the metabolism of normal cells promotes the metastasis of ovarian cancer cells
A systematic examination of the tumor and the tissue surrounding it -- particularly normal cells in that tissue, called fibroblasts -- has revealed a new treatment target that could potentially prevent the rapid dissemination and poor prognosis associated with high-grade serous carcinoma (HGSC), a tumor type that primarily originates in the fallopian tubes or ovaries and spreads throughout the abdominal cavity.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
White blood cells related to allergies may also be harnessed to destroy cancer cells
A new Tel Aviv University study finds that white blood cells which are responsible for chronic asthma and modern allergies may be used to eliminate malignant colon cancer cells.
Conversion of breast cancer cells into fat cells impedes the formation of metastases
An innovative combination therapy can force malignant breast cancer cells to turn into fat cells.
Breast cancer cells in mice tricked into turning into fat cells
As cancer cells respond to cues in their microenvironment, they can enter a highly plastic state in which they are susceptible to transdifferentiation into a different type of cell.
More Cancer Cells News and Cancer Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.