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:

Scientists have identified the presence of cancer-suppressing cells in pancreatic cancer
Researchers have identified cells containing a protein called Meflin that has a role in restraining the progression of pancreatic cancer.
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.
Brain cancer: Typical mutation in cancer cells stifles immune response
The exchange of a single amino acid building block in a metabolic enzyme can lead to cancer.
Researchers find prostate cancer drug byproduct can fuel cancer cells
A genetic anomaly in certain men with prostate cancer may impact their response to common drugs used to treat the disease, according to new research at Cleveland Clinic.
Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.
An index measures similarity between cancer cells and pluripotent stem cells
The new methodology measures tumor aggressiveness and the risk of relapse, helping doctors plan treatment, according to Brazilian scientists authors of a paper published in a special issue of the journal Cell.
More Cancer Cells News and Cancer Cells Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.