Researchers discover the feeding mechanism of cancer cells, essential for tumor growth

An international team led by researchers from the University of Cincinnati and Japanese universities Keio and Hiroshima has discovered the mechanism of energy production of cancer cells that promotes the growth of the nucleolus and causes rapid multiplication of tumors.

The results, published on August 1 in the newspaper Nature Cell Biology, could lead to the development of new cancer treatments that would stop tumor growth by reducing the energy supply of the nucleolus.

"The nucleolus is" the eye "of the cancerous storm that ravages patients' bodies, so being able to control the eye would really make a difference in cancer treatment," said Atsuo Sasaki, Ph.D. , badociate professor at the UC. College of Medicine and one of the principal investigators of the research team.

The nucleolus, located near the center of the nucleus, produces ribosomes. According to Sasaki, the discovery of nucleolar magnification in cancer cells occurred more than 100 years ago. Studies have since shown that nucleolus enlargement leads to a significant increase in the ribosome, propelling protein synthesis to mbad-produce cancer cells. But, how does the nucleolus produce a huge amount of ribosome in cancer cells is largely a mystery, he says.

"The enlargement of the nucleolus is a telltale sign of cancer, and its size has long been used as a criterion for determining the state of cancer progression in patients," Sasaki said. "Our research team now knows that the nucleolus expands rapidly by devouring Guanosine Triphosphate, or GTP, a nucleotide and one of the building blocks necessary for the creation of RNA, which is prevalent in cancer cells. . "

"We were surprised to discover that of all the types of energy that can be used for cell growth, it is the GTP that stings and plays the most crucial role in the increase of the ribosome badociated with the enlargement of the nucleolus. in cancer cells. It was a substantial discovery that would require a wide range of expertise to understand what it really meant, "adds Sasaki.

According to Sasaki, researchers have found a high level of inosine monophosphate dehydrogenase (IMPDH) in cancer cells, which accelerates the production of GTP and, in turn, fuels the growth of the nucleolus. This is a major step in solving the mystery surrounding the growth of nucleoli in cancer cells, he said.

To conduct the research, the multidisciplinary team focused on the energy production pathways in malignant brain tumors and glioblastoma, the most deadly type of brain cancer, on female models. animals, followed by cohort studies on human samples. The results showed a significant increase in GTP, which is a form of energy, in glioblastoma. Experts have taken a closer look at brain tumor cells and determined that the significantly elevated level of IMPDH in cancer cells accelerates the production of GTPs.

The close relationship between the IMPDH and the nucleolus was discovered and prompted the Sasaki team to develop a new method of metabolic badysis, which allowed researchers to obtain crucial data to demonstrate that GTP produced from IMPDH activities is used for ribosome synthesis of the nucleolus; This led to the discovery of a clear correlation between the suppression of glioblastoma cell growth and the inhibition of IMPDH, which prolonged the life of animal models.

"Thanks to our multi-disciplinary multinational collaboration and the hard work of the team, we have been able to understand the mechanism by which cancer cells divert GTP metabolism to take control of the nucleoli. research on GTP for the development of therapies to wipe out "the eye of cancer" in patients, "said Sasaki.