| 3 min read
Register for free to listen to this article
Listen with Speechify
0:00
3:00
BLOOMINGTON, Ind.—One of the most well-known hallmarks of cancer is the rapid, uncontrollable growth of cancer cells, which leads to tumors and metastasis. Recently, a team at Indiana University found a new way to study a molecule that plays a role in the growth of some cancers and neurodegenerative disorders—and in the rapid growth of fruit flies. The study, “Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth,” was published in the Proceedings of the National Academy of Sciences. The work was supported in part by the National Institute of General Medical Sciences of the National Institutes of Health, the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.
 
The molecule in question is L-2-hydroxyglutarate, or L-2HG, which is commonly regarded as an "oncometabolite," a molecule that can promote tumor formation and growth. L-2HG has been seen in tumor cells from patients with kidney and brain cancers (specifically gliomas and renal cell carcinomas), and in patients with L-2-hydroxyglutaric aciduria, a rare neurological disorder characterized by muscle weakness, seizures and damage to the parts of the brain responsible for muscle movement, speech, vision, emotion and memory. This study is the first one to show how L-2HG acts in a living system without cancer.
 
"We found that the same molecule implicated in human cancers is also produced by fruit flies during their larval stage," said senior author Jason M. Tennessen, an assistant professor in the IU Bloomington College of Arts and Sciences' Department of Biology. "The discovery is significant because it provides the first animal model to understand how these molecules function in healthy cells. If we can determine the function of this molecule in normal cells, we can better understand how it causes human disease."
 
"How the function of L-2GH differs between healthy and diseased tissues is poorly understood," Tennessen added. "In addition to establishing a new model for studying this cancer-related molecule, our study demonstrates that a compound previously regarded as a metabolic waste product actually functions in healthy animals."
 
As noted in the study, L-2GH “was recently discovered to control immune cell fate, thereby demonstrating that it has endogenous functions in healthy animal cells. Here, we find that the fruit fly, Drosophila melanogaster, also synthesizes high concentrations of L-2HG during normal larval growth … L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification and cell differentiation. “
 
Tennessen's lab made this discovery while working to develop fruit flies lacking dehydrogenase, an enzyme believed to fuel tumor growth. When they analyzed normal and mutant flies using metabolomics, the research team found the mutant flies stopped producing lactate and L-2HG.
 
Upon further analysis of the normal flies, Tennessen and his team discovered that flies usually produce L-2HG at high levels during their larval stage, in which they grow over 200 times in size over the course of several days. In addition, they found a mechanism that enables the flies to control the accumulation of L-2HG—an important factor, since these high levels of L-2HG are carefully controlled. If the precise factor by which this mechanism detects L-2HG levels and cuts off production when a sufficient amount is accumulated, it could potentially offer a new avenue for cancer research, should L-2HG levels prove to be similarly controllable in humans.
 
The next step, according to Tennessen, is to investigate precisely how L-2HG functions in healthy animals. "What happens if there's too much of it, or too little? Does it accelerate growth, or slow it down? Exactly what genes does it control? There’s a lot of important questions we can answer using the power of fly genetics," he concluded.
 
 
SOURCE: IU press release

About the Author

Related Topics

Loading Next Article...
Loading Next Article...
Subscribe to Newsletter

Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

Subscribe

Sponsored

A doctor wearing blue gloves and a white lab coat with a stethoscope around their neck holds a rendering of a digestive system on a glass pane with a swirled blue background.

Connecting the gut and liver to enhance drug development

Explore how a dual-organ microphysiological system connects human gut and liver tissue to bridge gaps in predicting how drugs behave in the body.
A syringe draws liquid from a glass vial, with several glass ampoules reflected on a glossy surface in the background

Turning up the heat: thermal analysis for biotherapeutics

Explore essential thermal stability techniques to ensure the safety, quality, and efficacy of biologic drugs.
A 3D-rendered image of a pink and white twisted RNA strand floating against a green, blurred cellular background.

Cutting the time and cost out of plasmid generation

Discover a hassle-free path to obtaining long, complex plasmid DNA.
Drug Discovery News March 2025 Issue
Latest IssueVolume 21 • Issue 1 • March 2025

March 2025

March 2025 Issue

Explore this issue