HMS Research Identifies Metabolic Enzyme that Facilitates Lung Cancer Growth

Researchers at the Harvard Medical School discovered that the enzyme GUK1 promotes lung cancer growth by boosting the metabolism of tumor cells, according to a Feb. 6 study published in Cell, a research publication.

Lung cancer researchers previously knew that tyrosine proteins could aid regulation of the metabolic process in cancer cells, but the new findings reveal that tyrosine directly promotes lung cancer growth by regulating enzymes like GUK1.

Though the disease is the leading cause of cancer-related deaths in the United States and worldwide, lung cancer’s molecular strategies of growth have remained difficult to pinpoint. This month’s HMS study sheds new light on lung cancer’s cellular mechanisms, according to Kiran Kurmi, an assistant professor at the University of Miami and co-first author of the HMS study.

The study shows that lung cancer cells “can chemically modify metabolic enzymes such as GUK1 to enhance their function and tumor growth,” he said.

The team used mouse models and human cancer cells to identify the relevant enzyme, using protein analysis to compile a list of possible target enzymes before arriving at GUK1.

The study is the first time the researchers were able to demonstrate that nucleotide metabolism directly regulates key growth enzymes, Kurmi said.

According to senior author Marcia C. Haigis, a professor of cell biology at HMS, it was unexpected that GUK1 emerged as the identified target.

GUK1 “was previously not well studied in cancer because it was thought of as a non-specific ‘housekeeping’ enzyme,” Haigis wrote in an email.

Haigis added that the “synergistic team” working on the project contributed to the success of the study, pointing to Kurmi’s biochemistry expertise and co-first author Jamie L. Schneider’s clinical experience as a thoracic oncologist at Mass. General Hospital.

Josephina Stampson, a postdoctoral research fellow studying cancer cell biology at the University of Leeds, said the study was well-executed and holds promise.

Studies like this are “helping all of us to understand more about the biology of these oncogenic fusions,” she said.

“The importance of this study is that overall, they found this metabolic kinase to be involved in other oncogene fusions, which is actually very, very important in terms of cancer biology,” Stampson added. “It suggests that it’s more of a widespread, universal kind of mechanism of how oncogenic fusions relate with metabolism to control tumor growth.”

Given that GUK1 serves as a key enzyme providing the cancer cells with metabolic support required for rapid and sustained growth, several experts said it could be a promising target for new lung cancer therapies.

However, it may still be too early to know whether GUK1 could serve as a viable target for lung cancer patients.

“Our work identified that GUK1 activation is important for certain subsets of lung cancer, but more work will need to be performed to know whether it is a specific target,” Haigis wrote.

—Staff writer Mana Tsuruta can be reached at mana.tsuruta@thecrimson.com. Follow her on X @ManaTsuruta.