Metabolite Drives Tumor Cell Development

The liver is a key organ that performs numerous vital activities in the body. It metabolizes nutrients, stores energy, controls blood sugar levels, and aids in the detoxification and removal of toxic components and medicines. Liver cancer is one of the most fatal types of cancer in the globe. Obesity, heavy alcohol intake, and hepatitis C infection are all risk factors for liver cancer. Early detection and proper therapy techniques are critical for improving liver cancer therapies and killing tumor cell.

Cancer is classified as a metabolic disorder

Scientists have made significant progress in comprehending the various aspects of cancer during the last decade. It has long been thought to be a problem with cell growth. There is, however, mounting evidence that cancer is a metabolic illness. Cancer develops when cells rearrange their metabolism to facilitate uncontrolled cell multiplication. How can cells alter their metabolism, and how does this alteration result in tumorigenicity? Researchers from the Biozentrum, University of Basel, lead by Professor Michael N. Hall, have uncovered a major driver of metabolic rewiring in liver cancer cells in a recent study published in “Cell.”

Arginine accumulation in liver carcinoma

When healthy liver cells transform into cancer cells, their behavior progressively changes. They alter their metabolism to expand as quickly as possible, consuming significantly more glucose than normal cells and increasing food intake.

“We investigated liver tumor samples from mice and patients and found elevated levels of arginine, although cancer cells produce less or none of this amino acid. The tumor cells accumulate high levels of arginine by increasing its uptake and suppressing its consumption,” says lead author Dr. Dirk Mossmann. “Furthermore, we found that the high levels of arginine are necessary for tumor development, independently of the amino acid’s role in protein synthesis. This then begged the question, how does arginine lead to tumorigenicity?”

Arginine’s function in tumor growth

At high quantities, arginine binds to a particular factor, which causes metabolic reprogramming and promotes tumor growth by regulating metabolic gene expression. As a result, tumor cell return to an undifferentiated embryonic cell state and can divide indefinitely. Interestingly, boosting arginine absorption benefits tumor cells in another way. “Our immune cells rely on arginine to function properly,” Mossmann says. “Therefore, depleting arginine in the tumor environment helps the tumor cell escape the immune system.”

Implications for liver cancer diagnosis and treatment

What does this signify for cancer treatment? Rather of decreasing arginine, the scientists recommend targeting a specific arginine-binding component. “When treating liver tumors with the anticancer drug indisulam, we induce the degradation of this factor and thus prevent metabolic reprogramming” , according to Mossmann. Via this route, one can avoid unwanted side effects of reducing overall arginine levels, like harming immune cells that need arginine to work properly.” Furthermore, metabolic changes such as elevated arginine levels may act as biomarkers for early detection of cancer, which is critical for successful cancer treatment and patient survival.

More Information: Arginine reprograms metabolism in liver cancer via RBM39, Cell Press

https://doi.org/10.1016/j.cell.2023.09.011