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Most cancers cells are relentless of their quest to develop and divide, typically rewiring their metabolism and modifying RNA to remain one step forward. Now, researchers on the UCLA Well being Jonsson Complete Most cancers Heart have recognized a single protein, IGF2BP3, that hyperlinks these two processes collectively in leukemia cells. The protein shifts how cells break down sugar, favoring a quick however inefficient vitality pathway, whereas additionally altering RNA modifications that assist produce the proteins leukemia cells must survive and multiply.
The invention, printed in Cell Experiences, positions IGF2BP3 as a “master switch” in leukemia, linking metabolism and RNA regulation, processes lengthy thought to function independently. Understanding this connection may pave the way in which for brand new therapies geared toward chopping off the vitality and survival pathways that most cancers cells rely on.
“We expected IGF2BP3 might control RNA, but what we weren’t expecting was how strongly it also reshaped metabolism,” mentioned Dr. Dinesh Rao, professor of pathology and laboratory drugs on the David Geffen Faculty of Drugs at UCLA and senior creator of the examine.
“That connection hadn’t been seen before and could be critical to how cancer cells gain their advantage. By uncovering this link, we now have a clearer picture of how leukemia sustains itself. If we can block this rewiring, we might be able to cut off both the energy supply and the survival signals cancer cells rely on.”
Rao and his lab have been learning IGF2BP3 for practically a decade and located that it’s important for the survival of leukemia cells. The protein belongs to a household of RNA-binding proteins which are usually lively solely on the earliest phases of human improvement. After start, their exercise largely shuts down, however in some cancers—together with leukemia, mind tumors, sarcomas, and breast cancers—IGF2BP3 switches again on.
The crew has beforehand proven that IGF2BP3 is crucial for an particularly aggressive subtype of pediatric acute lymphoblastic leukemia. Mice engineered to lack the protein had been immune to creating leukemia, but remained in any other case wholesome, suggesting IGF2BP3 is uniquely tied to most cancers biology. The rewiring of mobile metabolism has lengthy been a central focus in most cancers analysis, and Rao’s crew started to discover whether or not IGF2BP3 additionally shapes how leukemia cells course of vitality.
To know how IGF2BP3 influences these processes, Rao and his crew used a specialised expertise known as the Seahorse assay, which measures how cells use oxygen and produce acid, primarily placing cells “on a treadmill” to see how they burn vitality.
They discovered when leukemia cells had been stripped of IGF2BP3, their most popular vitality pathway, glycolysis, dropped sharply. Glycolysis is a fast however wasteful method of breaking down sugar, typically favored by most cancers cells as a result of it produces the constructing blocks they should multiply.
Additional experiments traced how sugar was being processed contained in the cell. The crew found that ranges of S-adenosyl methionine, or SAM, a vital molecule that donates chemical tags used to change RNA, fell dramatically with out IGF2BP3. In consequence, the variety of RNA methylation marks additionally decreased, revealing that IGF2BP3 does not simply regulate genes, but in addition rewires metabolism in ways in which feed again into RNA management.
As a closing step, the researchers used specifically engineered mice that lacked the IGF2BP3 gene. Once they reintroduced the human model of the protein, the adjustments in metabolism and RNA regulation returned, confirming IGF2BP3’s central position in driving these processes.
“These experiments revealed a chain reaction,” mentioned Dr. Gunjan Sharma, a postdoctoral scholar within the Rao laboratory. “When we removed IGF2BP3, it didn’t just change how cells used energy. It also disrupted their chemical balance and the way their RNA was regulated. That’s how we realized IGF2BP3 links metabolism and RNA control in leukemia.”
The findings counsel that IGF2BP3 permits leukemia cells to take a much less environment friendly metabolic pathway not as a result of it supplies extra vitality, however as a result of it provides constructing blocks and RNA modifications that reinforce most cancers cell survival.
“In a way, IGF2BP3 is a master planner,” Sharma defined. “It rewires both energy use and RNA control to keep leukemia cells growing where normal cells wouldn’t.”
Whereas the examine centered on leukemia, the researchers consider the implications might lengthen to many different cancers.
“While leukemia is the model where we’re seeing this most clearly, the broader message is that cancer cells across the board may be using similar strategies,” mentioned Rao, who’s a member of the UCLA Well being Jonsson Complete Most cancers Heart and the Eli and Edythe Broad Heart of Regenerative Drugs and Stem Cell Analysis at UCLA. “This means the insights from our research could eventually help us design therapies that target not only leukemia but also other cancers that exploit the same pathways.”
Excessive ranges of IGF2BP3 may additionally function a biomarker, the researchers famous, serving to to establish cancers which will reply to therapies disrupting RNA modifications or SAM manufacturing. Rao’s lab is now testing small molecules that block IGF2BP3, with essentially the most promising methods doubtless pairing these inhibitors with medicine that intrude with most cancers metabolism.
Extra info:
Cell Experiences Drugs (2025). DOI: 10.1016/j.celrep.2025.116330
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College of California, Los Angeles
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How a single protein rewires leukemia cells to gasoline their progress (2025, September 26)
retrieved 27 September 2025
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