Breakthrough in Tumor Energy Metabolism Offers Hope for Cancer Treatments
Understanding Cancer Cell Metabolism
Tumors are marked by uncontrolled cellular growth, which is driven by a series of metabolic reactions that produce the energy and molecular components necessary for replication. This phenomenon, known as cancer cell metabolism, depends on various proteins and enzymes engaged in metabolic pathways. Researchers are now exploring methods to target crucial metabolic proteins to “reprogram” cancer cell metabolism, thereby inhibiting tumor growth and enhancing the effectiveness of treatments.
Key Findings from Collaborative Research
A research team comprising members from Oregon State University, The University of Central Florida, and New York University has identified a significant protein modification that governs the proliferation and survival of tumor cells. The study focused on neurofibromatosis type 2 (NF2), a disorder characterized by tumors within the nervous system. The tumor cells in this condition generate a potent oxidant known as peroxynitrite, which interacts with the amino acid tyrosine in proteins. This modification may lead to changes in protein function and influence cellular metabolism.
Using primary tumor cells from NF2 patients, alongside human and mouse cell models, the researchers discovered elevated levels of peroxynitrite in affected cells. Furthermore, peroxynitrite was found to modify essential metabolic enzymes to enhance energy production. These findings underscore the role of peroxynitrite in redirecting cancer cell metabolism towards tumor growth and proliferation.
Insights from the Research Team
The study, published in the Journal of Biological Chemistry, highlights the metabolic adaptations of tumor cells. “To sustain persistent growth, tumor cells change the way they produce energy and building blocks, presenting a metabolic phenotype distinct from that of normal cells,” stated Maca Franco, a professor of biochemistry and biophysics at OSU’s College of Science. Franco elaborated that peroxynitrite, the most potent oxidant generated by cells, regulates the metabolic alterations in nervous system tumor cells and supports their growth. The research suggests that certain proteins, when nitrated, acquire new functions that may influence tumor growth.
Potential for Future Cancer Therapies
The researchers propose that the proteins modified by peroxynitrite could serve as promising molecular targets for novel drug development aimed at NF2 and other cancers. By inhibiting these modified proteins, therapies could potentially target tumor cells directly while minimizing harm to healthy tissues.
References
Pestoni, J. C. et al. Peroxynitrite supports a metabolic reprogramming in merlin-deficient Schwann cells and promotes cell survival. J. Biol. Chem. 294, 11354–11368 (2019).
Franco, M. Researchers take key step toward cancer treatments that leave healthy cells unharmed. EurekAlert! (2019).
Picture credit: Maca Franco, OSU College of Science.