Nav: Home

Researchers uncover new target to stop cancer growth

June 21, 2018

Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes--tiny, membrane-bound packages containing proteins and RNAs that stimulate tumor progression. The study, which will be published June 21 in the Journal of Cell Biology, could lead to new therapies that stop tumor growth and metastasis by halting exosome production.

Cancer cells produce large numbers of exosomes, which contribute to tumor progression in many different ways. They can transfer cancer-causing oncogenes to neighboring cells to increase their proliferation; they can contain proteins that reorganize the cancer cells' surroundings and allow them to spread to other tissues; and they can contain signaling factors that disrupt the body's ability to mount an immune response against the tumor.

A team led by Thomas F.J. Martin of the University of Wisconsin-Madison with Scott W. Messenger as lead author found that calcium--which is often increased in cancer cells--stimulated the secretion of exosomes from aggressive breast cancer cells. Exosome release depended on a calcium-binding protein called Munc13-4; removing this protein, or replacing it with a mutant version unable to bind calcium, prevented breast cancer cells from releasing exosomes in response to calcium.

Munc13-4 levels are often elevated in human breast, pancreatic, and lung tumors. Martin and colleagues found that lung and pancreatic cancer cells increased their levels of Munc13-4 and released more exosomes as they became more aggressive.

Exosomes are formed inside large cellular organelles called multivesicular bodies. These organelles then fuse with the cell's plasma membrane to release exosomes outside of the cell. Messenger et al. found that Munc13-4 works with another protein called Rab11 to promote the development of multivesicular bodies capable of fusing with the plasma membrane and releasing exosomes.

Exosomes released from cancer cells carry an enzyme called MT1-MMP, which degrades the extracellular matrix surrounding cancer cells. This helps the cancer cells disperse around the body to form secondary metastatic tumors.

When Martin and colleagues depleted Munc13-4, they reduced the release of MT1-MMP-containing exosomes from breast cancer cells and inhibited the cells' ability to degrade the extracellular matrix.

"Overall, we think that increased expression of Munc13-4, combined with elevated calcium levels, drives enhanced exosome release by highly aggressive cancer cells, and that Munc13-4 is a potential target for therapeutic intervention," Martin says.
-end-
Messenger et al., 2018. J. Cell Biol.http://jcb.rupress.org/cgi/doi/10.1083/jcb.201710132?PR

About the Journal of Cell Biology

The Journal of Cell Biology (JCB) features peer-reviewed research on all aspects of cellular structure and function. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JCB makes all of its content free online no later than six months after publication. Established in 1955, JCB is published by the Rockefeller University Press. For more information, visit jcb.org.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JCB on Twitter at @JCellBiol and @RockUPress.

Rockefeller University Press

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.