Nav: Home

Newly discovered cellular pathway may lead to cancer therapies

June 15, 2017

Scientists have discovered a new cellular pathway that can promote and support the growth of cancer cells. In a mouse model of melanoma, blocking this pathway resulted in reduction of tumor growth. The study, which appears in Science, offers a novel opportunity to develop drugs that could potentially inhibit this pathway in human cancer cells and help control their growth.

"We had been studying components of this pathway for several years," said senior author Dr. Andrea Ballabio, professor of molecular and human genetics at Baylor College of Medicine and Texas Children's Hospital in Houston, Texas, and director of the Telethon Institute of Genetics and Medicine in Naples, Italy. "We know that the pathway is important for normal cells to carry their activities as it is involved in regulating metabolism, that is, how cells process nutrients to obtain energy and how cells use energy to grow. In this study we wanted to learn more about how the pathway regulates its activity."

Pathways involved in cellular metabolism typically regulate themselves, meaning that some components of the pathway control each other's activities. "We suspected that the pathway was autoregulated, and we confirmed it in this study. Our experimental approaches showed that there is a feedback loop within the path that allows it to control itself."

An important pathway for normal cellular activities


Ballabio and his colleagues studied the role of the pathway in two normal cellular activities; how cells respond to physical exercise and how they respond to nutrient availability. In terms of physical exercise, the researchers determined that the self-regulating mechanism they discovered is essential for the body builder effect.

"Some athletes take the aminoacid leucine or a mixture of aminoacids immediately after exercising, which promotes protein synthesis that leads to muscle growth. This is the body builder effect," Ballabio said. "When we genetically engineered mice to lack the pathway, we lost the body builder effect."

The researchers had a group of normal mice and another of mice lacking the pathway. Both groups were set to exercise and fed leucine immediately after. While normal mice showed enhanced protein synthesis, the mice without the pathway did not.

"In healthy organisms, this pathway also allows cells to adapt more efficiently to nutrient availability," Ballabio said. "For example, when transitioning from a period of starvation to one in which food is available, cells need to switch from catabolism to anabolism. Starvation promotes catabolism - the breakdown of nutrients to obtain energy to function - and eating promotes anabolism - the buildup of molecules, such as proteins. The feedback we discovered mediates the switch from catabolism to anabolism, allowing organisms to adapt to food availability."

An important pathway for cancer growth


The scientists also studied the role this pathway might play in cancer cells. They discovered that overactivation of this pathway, which is observed in some types of cancer such as renal cell carcinoma, melanoma and pancreatic cancer, is important to promote and support the growth of cancer cells in culture and animal models.

"Most importantly, we demonstrated in our study that blocking the pathway resulted in reduction of tumor growth in an experimental model of human melanoma transplanted into mice," Ballabio said. "I am most excited about the future potential therapeutic applications of this discovery against cancer. Developing pharmacological treatments that interfere with this pathway might one day help stop tumor growth."

Rare disease discoveries can improve our understanding of common diseases


"Our lab focuses on rare genetic diseases, such as lysosomal storage genetic disorders, in which we originally studied this pathway," Ballabio said. "Then, we discovered that the pathway is also important in cancer. Our and other researchers' work on rare genetic diseases sometimes produces findings that can potentially be applicable to more common diseases, such as cancer."
-end-
For a complete list of the authors of this work and their affiliations, please refer to the published article.

This study was supported by grants from the Italian Telethon Foundation (TGM11CB6); European Research Council Advanced Investigator grant no. 250154 (CLEAR) and no. 341131 (InMec); U.S. National Institutes of Health (R01-NS078072); and the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) IG 2015 Id 17639 and IG 2015 Id 17717.

Baylor College of Medicine

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related 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".