They found the hidden energy centers of cancer and learned how to dissolve them

Their study was published in Nature CommunicationsIt reveals that RNA, normally known to transmit genetic messages, can be hijacked to build fluid-like “droplet centers” inside the cell nucleus. These droplets act as command centers that activate growth-related genes. The team not only observed this phenomenon, but also developed a molecular switch that can melt these axons on demand, effectively cutting off the cancer growth mechanism at its core.

RNA becomes the originator of cancer

The researchers focused on a rare kidney cancer called transitional renal cell carcinoma (tRCC), which primarily affects children and young adults and currently lacks effective treatments. This cancer is caused by a tumor fusion of TFE3 – abnormal hybrid genes that arise when chromosomes break and fuse incorrectly.

Until now, scientists don’t fully understand how these fusion proteins make tRCC so aggressive. The Texas A&M University team found that fusions recruit RNA to serve as a structural framework. Instead of simply carrying messages, RNA molecules assemble into droplet-like condensates that hold biomolecules together. These droplets then act as transcriptional hubs, activating genes that promote tumor growth.

“RNA itself is not just a passive messenger, but an active player that helps build these condensates,” said Yun Huang, Ph.D., a professor at the Texas A&M Health Institute for Biosciences and Technology and senior author.

The team also identified an RNA-binding protein called PSPC1, which stabilizes these droplets and makes them more effective at stimulating tumor formation.

Mapping the hidden machinery of cancer

To uncover how this process works, the researchers used a range of cutting-edge molecular biology tools:

• Gene editing with CRISPR technology To “tag” fusion proteins in patient-derived cancer cells, allowing them to track exactly where these proteins go.
• Peace-seqa next-generation sequencing method that measures newly synthesized RNA, showing which genes are turned on or off during droplet formation.
• Cut, tag and RIP-seq To map where fusion proteins bind DNA and RNA, revealing their precise targets.
• Proteins to index proteins pulled into droplets, identifying PSPC1 as a major partner.

By layering these techniques, the researchers have built the clearest picture yet of how TFE3 hijacks RNA to build cancer growth centers.

Dissolving the axons that drive tumors

Discovery alone was not enough. The team wanted to know: If droplets are the driver of cancer, can we stop them?

To test this, they designed a chemical tool based on nanobodies – essentially a designer molecular switch. Here’s how it works:

• The nanobody (a small portion of the antibody) is combined with a solvent protein.
• The nanobody attaches to cancer-causing fusion proteins.
• When activated by a chemical catalyst, the solvent dissolves the droplets, disassembling the axons.

The result? It stops tumor growth in both laboratory-grown cancer cells and mouse models.

“This is exciting because tRCC has very few effective treatment options today,” said Yubin Zhu, MD, professor and director of the Center for Translational Cancer Research. “Targeting the formation of condensates gives us a whole new angle to attack cancer, one that has not been addressed by conventional drugs. It opens the door to more precise and potentially less toxic treatments.”

Beyond kidney cancer: a new treatment paradigm

For the research team, the most powerful part of the study was not just watching RNA build these hubs, but seeing that they could be dismantled.

“By mapping how these fusion proteins interact with RNA and other cellular partners, we not only explain why this cancer is so aggressive, we also reveal vulnerabilities that can be exploited therapeutically,” said Li Guo, Ph.D., a research assistant professor at the Institute of Bioscience and Technology.

Because many childhood cancers are also driven by fusion proteins, the implications extend beyond tRCC. A tool that can dissolve these condensates could represent a general strategy for cutting out the cancer’s engine chambers at the source.

Why is this important?

tRCC accounts for approximately 30% of kidney cancer cases in children and adolescents, yet treatment options remain scarce and outcomes are often poor. This breakthrough provides an explanation for how cancer regulates its molecular machinery and a potential way to dismantle them.

“This research highlights the power of basic science to generate new hope for young patients facing devastating diseases,” Huang added.

Just as cutting off power to a coworking center stops all activity, dissolving a cancer’s “droplet axons” can stop its ability to grow. By revealing how RNA builds these structures — and by finding a way to break them down — Texas A&M University Health researchers have opened a promising new path toward treating one of the most challenging types of childhood cancers.