Journal News

JBC: Starving triple-negative breast cancer slows growth

Jonathan Griffin
September 01, 2019

A team of Brazilian researchers has developed a strategy that slows the growth of triple-negative breast cancer cells by cutting them off from two major food sources.

Panel Heterogeneous presentation of glutaminase (red) and CPT1 (green) is shown across several TNBC cell lines. The cell line in the top right panel is resistant to the drug CB-839. A study by dos Reis et al. suggests that these cells survive treatment by increasing fatty acid (purple) consumption in their mitochondria (yellow). Douglas Adamoski/Brazilian Biosciences National Laboratory

About 15% to 20% of all breast cancers are triple-negative, and the type is most common in African American women. These tumors lack estrogen and progesterone receptors and HER2 protein that are present in other breast cancers and permit certain targeted therapies. Every TNBC tumor has a different genetic makeup, so finding new markers to guide treatment has been difficult.

Sandra Martha Gomes Dias is a cancer researcher at the Brazilian Biosciences National Laboratory in Campinas, Brazil. “There is intense interest in finding new medications that can treat this kind of breast cancer,” she said. “TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer, mainly because there are fewer targeted medicines that treat TNBC.”

In a new study in the Journal of Biological Chemistry, Dias and colleagues demonstrate that in addition to glutamine, a well-known cancer food source, TNBC cells can use fatty acids to grow and survive. When inhibitors that block both glutamine and fatty acid metabolism were used in concert, Dias said, TNBC growth and migration slowed.

To maintain their ability to grow at a breakneck pace, cancer cells often consume nutrients at a higher rate than normal cells. Glutamine, the most abundant amino acid in plasma, is one of these nutrients. Some cancers become heavily reliant on this versatile molecule, Dias said, as it offers energy, carbon, nitrogen and antioxidant properties, all of which support tumor growth and survival.

The drug telaglenastat, also known as CB-839, prevents glutamine processing and is in clinical trials to treat TNBC and other tumor types. CB-839 deactivates the enzyme glutaminase, preventing cancer cells from breaking down and reaping the benefits of glutamine. However, recent research has shown that some TNBC cells can resist its effects.

To see if alterations in gene expression could explain how these cells survive, Dias said, her team exposed TNBC cells to CB-839 and then defined those that were resistant and those that were sensitive to the drug and sequenced their RNA.

In the resistant cells, molecular pathways related to the processing of lipids were altered, Dias said. In particular, levels of the enzymes CPT1 and CPT2, critical for fatty acid metabolism, were increased.

“CPT1 and 2 act as gateways for the entrance of fatty acids into mitochondria, where they will be used as fuel for energy production,” Dias said. “Our hypothesis was that closing this gateway by inhibiting CPT1 in combination with glutaminase inhibition would decrease growth and migration of CB-839-resistant TNBC cells.”

The double inhibition slowed proliferation and migration in resistant TNBC cells more than individual inhibition of either CPT1 or glutaminase. Dias said these results provide new genetic markers to better guide drug choice in patients with TNBC.

Jonathan Griffin

Jonathan Griffin is a science communicator for all ASBMB journals. Follow him on Twitter.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Science

Science highlights or most popular articles

Life's little oscillations
News

Life's little oscillations

April 05, 2020

Concentrations of molecules rise and fall, genes switch on and off, and circadian clocks keep time. These biochemical fluctuations are crucial for myriad biological needs, and cells couldn't function without them.

A small trial finds that hydroxychloroquine is not effective for treating coronavirus
News

A small trial finds that hydroxychloroquine is not effective for treating coronavirus

April 05, 2020

Despite the recent approval of this drug for use against COVID-19, questions remain as to the efficacy of this treatment.

Team Cryo ices Mass Spec’s hopes in JBC Methods Madness tourney
Journal News

Team Cryo ices Mass Spec’s hopes in JBC Methods Madness tourney

April 03, 2020

In the inaugural JBC Methods Madness Tournament, cryo­–EM/ET gave structural biologists around the world something to cheer about, beating mass spectrometry 51% to 49% —​ a margin thinner than shaved ice. 

A small army of researchers races to build a coronavirus interactome
News

A small army of researchers races to build a coronavirus interactome

April 01, 2020

Scientists at eight institutions in the U.S. and Europe have used a protein interaction map to identify 69 drugs that might work against SARS-CoV-2, the virus that causes COVID-19.

Parkinson's  Awareness Month
Health Observance

Parkinson's Awareness Month

April 01, 2020

It is the second-most common progressive neurodegenerative disease, occurring in 1% of people over the age of 60 and in 5% of people over 85.

Multiomics meets antimalarials
Journal News

Multiomics meets antimalarials

March 31, 2020

Researchers in Australia use an innovative multiomics approach to analyze a new drug against malaria parasites.