Nav: Home

New study explains how very aggressive cancer cells use energy to divide, move

June 14, 2016

ANN ARBOR, Mich. -- Cancer cells and normal cells both divide and move, but with cancer cells it's like they're on steroids: everything is bigger, faster, more.

A new study explains how cancer cells use energy to fuel this switch between motion and proliferation. The researchers identified for the first time a connection between a cancer gene that controls motility and how cancer cells metabolize energy to move and divide so quickly.

Researchers looked at inflammatory breast cancer cells and found the gene RhoC interacts with the cell's machinery at a molecular level to regulate how it produces energy. RhoC directs the cells to generate energy from glucose quickly. This wiring then drives the cancer cells to move faster than normal. RhoC also controls how cancer cells use another nutrient, the amino acid glutamine.

"This is a vulnerability for aggressive cancer cells that we are prepared to exploit. We have definitely found an entry point that lies at the heart of the cancer cell's ability to use energy," says Sofia D. Merajver, M.D., Ph.D., scientific director of the breast oncology program at the University of Michigan Comprehensive Cancer Center and the senior author on the paper.

"Because cancer cells are abnormal, they have limited options to survive. They need to leverage every advantage. When we find an opportunity like this to attack how cancer cells function, we create an opportunity to help destroy the cancer."

Inflammatory breast cancer is a very aggressive form of the disease that disproportionately affects young women and African American women. Instead of a lump, inflammatory breast cancer causes swelling and changes in the skin around the breast. It often has spread beyond the breast by the time it's diagnosed.

Merajver's lab has previously found that RhoC is a key driver of inflammatory breast cancer. It's also linked to more advanced and aggressive types of lung, melanoma, pancreatic and bladder cancers.

The new findings, published in the Journal of Biological Chemistry, identify several key metabolites that are specifically altered by RhoC. These metabolites ultimately control how much energy is available within the cell. This is the first study linking an oncogene involved in cancer cell motility to the metabolic processes necessary to carry out its orders to move and spread.

"We are very excited to discover a connection between a known metastasis-causing gene and alterations to the metabolic characteristics of the cells. RhoC seems to cause very specific and robust changes in the inflammatory breast cancer model that differ from not only normal-like cells, but also other types of breast cancer," says study co-first author Joel A. Yates, Ph.D., a senior postdoctoral research fellow at U-M.

The researchers suggest that these metabolic and molecular vulnerabilities could be explored as potential targets for therapy. The concept expands on personalized medicine and genetic sequencing to include personalized metabolomics - a process in which treatments could be prescribed based on how much of certain chemicals are produced in cancer cells.

"Through metabolomics we can describe exactly what is happening at the molecular level even if we do not know exactly all the connections between the signaling proteins in the cell," Merajver says. "Gene sequencing would reveal RhoC is involved, but it wouldn't necessarily point us to the right target. It wouldn't tell us how things are wired."

The researchers plan to conduct additional experiments to understand which enzymes are most critical and could provide a good target for potential treatment. In addition, they are working with teams at U-M to develop RhoC inhibitors.

"I have wanted to cure inflammatory breast cancer since medical school, when I saw my first patient with it," Merajver says. "This is why basic science is important. It's essential to understand the biology and the exact mechanisms so that we can find the right target to halt this devastating disease."
-end-
Funding for this work is from: Metavivor Foundation, Avon Foundation, Breast Cancer Research Foundation, James S. McDonnell Foundation, Liz and Eric Lefkofsky Innovative Research Fund, National Institutes of Health grants T32 CA140044, 5T32 GM008353, K25 DK092558, P30 CA046592 and U24 DK097153

Reference: Journal of Biological Chemistry, doi: 10.1074/jbc.M115.703959

University of Michigan Health System

Related Breast Cancer Articles:

Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
Blood test offers improved breast cancer detection tool to reduce use of breast biopsy
A Clinical Breast Cancer study demonstrates Videssa Breast can inform better next steps after abnormal mammogram results and potentially reduce biopsies up to 67 percent.
Surgery to remove unaffected breast in early breast cancer increases
The proportion of women in the United States undergoing surgery for early-stage breast cancer who have preventive mastectomy to remove the unaffected breast increased significantly in recent years, particularly among younger women, and varied substantially across states.
Breast cancer patients with dense breast tissue more likely to develop contralateral disease
Breast cancer patients with dense breast tissue have almost a two-fold increased risk of developing disease in the contralateral breast, according to new research from The University of Texas MD Anderson Cancer.
Some early breast cancer patients benefit more from breast conservation than from mastectomy
Breast conserving therapy (BCT) is better than mastectomy for patients with some types of early breast cancer, according to results from the largest study to date, presented at ECC2017.
One-third of breast cancer patients not getting appropriate breast imaging follow-up exam
An annual mammogram is recommended after treatment for breast cancer, but nearly one-third of women diagnosed with breast cancer aren't receiving this follow-up exam, according to new findings presented at the 2016 Annual Clinical Congress of the American College of Surgeons.
Low breast density worsens prognosis in breast cancer
Even though dense breast tissue is a risk factor for breast cancer, very low mammographic breast density is associated with a worse prognosis in breast cancer patients.
Is breast conserving therapy or mastectomy better for early breast cancer?
Young women with early breast cancer face a difficult choice about whether to opt for a mastectomy or breast conserving therapy (BCT).
Breast density and outcomes of supplemental breast cancer screening
In a study appearing in the April 26 issue of JAMA, Elizabeth A.
Full dose radiotherapy to whole breast may not be needed in early breast cancer
Five years after breast-conserving surgery, radiotherapy focused around the tumor bed is as good at preventing recurrence as irradiating the whole breast, with fewer side effects, researchers from the UK have found in the large IMPORT LOW trial.

Related Breast Cancer Reading:

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

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#513 Dinosaur Tails
This week: dinosaurs! We're discussing dinosaur tails, bipedalism, paleontology public outreach, dinosaur MOOCs, and other neat dinosaur related things with Dr. Scott Persons from the University of Alberta, who is also the author of the book "Dinosaurs of the Alberta Badlands".