Newly discovered cellular pathway may lead to cancer therapies

June 15, 2017, Baylor College of Medicine

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 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 , the mice without the pathway did not.

"In healthy organisms, this pathway also allows cells to adapt more efficiently to ," 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 . 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 ."

Rare disease discoveries can improve our understanding of common diseases

"Our lab focuses on , such as lysosomal storage genetic disorders, in which we originally studied this pathway," Ballabio said. "Then, we discovered that the 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 ."

Explore further: How to reap the benefits of exercise: It's in the genes

More information: "Transcriptional activation of RagD GTPase controls mTORC1 and promotes cancer growth," science.sciencemag.org/cgi/doi … 1126/science.aag2553

Related Stories

How to reap the benefits of exercise: It's in the genes

January 10, 2017
An international team of scientists at Baylor College of Medicine, the Telethon Institute of Genetics and Medicine in Naples, Italy and other institutions has discovered that the gene TFEB is a major regulator of muscle function ...

Study of blood vessel growth may open new pathway to therapies

May 4, 2017
A new Yale-led study detailing how blood vessels develop could lead to novel treatments of cardiovascular diseases as well as cancer.

Comprehensive cancer study assesses potential targets for personalized medicine and finds new ones

May 18, 2017
Looking to improve cancer treatment, a multi-institutional research team has taken a comprehensive approach to evaluating which molecular changes in cancer cells are most likely involved in the development of the disease. ...

Scientists discover metabolic pathway that drives tumor growth in aggressive cancers

March 2, 2017
Mount Sinai researchers have discovered that a rheumatoid arthritis drug can block a metabolic pathway that occurs in tumors with a common cancer-causing gene mutation, offering a new possible therapy for aggressive cancers ...

Blocking known cancer driver unexpectedly reveals a new tumor-promoting pathway

May 17, 2016
While investigating a potential therapeutic target for the ERK1 and 2 pathway, a widely expressed signaling molecule known to drive cancer growth in one third of patients with colorectal cancer, University of California San ...

Recommended for you

Developing an on-off switch for breast cancer treatment

August 17, 2018
T-cells play an important role in the body's immune system, and one of their tasks is to find and destroy infection. However, T-cells struggle to identify solid, cancerous tumors in the body. A current cancer therapy is using ...

Scientists discover new method of diagnosing cancer with malaria protein

August 17, 2018
In a spectacular new study, researchers from the University of Copenhagen have discovered a method of diagnosing a broad range of cancers at their early stages by utilising a particular malaria protein that sticks to cancer ...

Pregnant? Eating broccoli sprouts may reduce child's chances of breast cancer later in life

August 16, 2018
Researchers at the University of Alabama at Birmingham have found that a plant-based diet is more effective in preventing breast cancer later in life for the child if the mother consumed broccoli while pregnant. The 2018 ...

Three scientists share $500,000 prize for work on cancer therapy

August 15, 2018
Tumors once considered untreatable have disappeared and people previously given months to live are surviving for decades thanks to new therapies emerging from the work of three scientists chosen to receive a $500,000 medical ...

PARP inhibitor improves progression-free survival in patients with advanced breast cancers

August 15, 2018
In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over ...

New clues into how 'trash bag of the cell' traps and seals off waste

August 15, 2018
The mechanics behind how an important process within the cell traps material before recycling it has puzzled scientists for years. But Penn State researchers have gained new insight into how this process seals off waste, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.