Researchers at Umeå University in Sweden have uncovered a previously unknown biological mechanism that allows aggressive triple-negative breast cancer to fine-tune its protein production, a discovery that deepens scientific understanding of how tumors grow, adapt and survive. The findings also open new avenues for the development of future cancer treatments.
The study, led by Francesca Aguilo, an associate professor at Umeå University’s Department of Molecular Biology, identifies a critical control point in cancer cells that could potentially be exploited therapeutically. “We have found a critical control point that, when disturbed, can tip the balance against cancer,” Aguilo said.
All cells rely on ribosomes—microscopic molecular factories—to translate genetic instructions from RNA into proteins essential for cellular function. These ribosomes are intricate structures composed of ribosomal RNA and proteins, equipped with built-in regulatory systems to ensure accurate protein production. Disruption of these systems has long been linked to diseases, including cancer.
The researchers focused on ribosomal RNA, which contains numerous chemical modifications that help ribosomes operate efficiently. One key modification, known as 2′-O-methylation (Nm), is regulated by the enzyme fibrillarin. The study reveals that fibrillarin plays a central role not only in ribosome assembly but also in determining which proteins a cell ultimately produces.
According to the findings, fibrillarin works in concert with a ribosomal protein called RPS28 to form specialized ribosomes with distinct functional properties. When fibrillarin is absent, RPS28 is also lost, resulting in a heterogeneous population of ribosomes. This imbalance alters protein production patterns in ways that can promote cancer development, particularly in aggressive forms such as triple-negative breast cancer.
“Cancer is not only about mutated genes, but also about how cells control the amount and type of proteins that are produced,” Aguilo explained, underscoring the broader implications of the research.
While the findings are still at an early, preclinical stage, the researchers say the study highlights a promising new direction for cancer therapy—targeting tumors as diseases driven by misregulated protein production rather than focusing solely on genetic mutations.
The research was conducted in collaboration with several European universities and has been published in the scientific journal Cancer Letters. Funding was provided by the Swedish Research Council, the Swedish Cancer Society, and the Knut and Alice Wallenberg and Kempe Foundations, among others.
