A new research report from Uppsala University suggests that down-regulating synthesis of new ribosomes, an organelle inside our cells that create new proteins that serve as building blocks for cell replication, may slow cancer growth. It is known that the metastatic process is helped by the synthesis of new ribosomes as this increase in number is necessary for continued growth.
The study results open the possibility for new treatment strategies for advanced cancers, according to the scientists whose study (“Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease”) appears in Nature Communications.
“Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution of Epithelial-to-Mesenchymal Transition (EMT), a migratory cellular program associated with development and tumor metastasis, is fueled by upregulation of ribosome biogenesis during G1/S arrest,” the investigators wrote.
As tumors progress towards advanced stages with continual growth, they dedifferentiate (losing their specialized characteristics), become more aggressive, and lose the cellular functions of the origin tissue. They also acquire the migratory capacity that allows the tumor to metastasize to distant sites in the body, eventually causing patient death. “Until recently, ribosomes have been considered to play only passive roles during the production of proteins. Our study shows that ribosomes potentially have complex, active roles and suggests that more attention should be given to understanding how ribosomes contribute to cell physiology in health and disease states,” said Theresa Vincent, PhD, group leader at the department of immunology, genetics, and pathology at Uppsala University.
The study demonstrated that by inhibiting the formation of new ribosomes, aggressive and hormone insensitive tumors could be partially reverted to a benign and non-metastatic type. “We used a small molecule called CX-5461 to inhibit ribosome biogenesis in mouse models of human tumors. We found that primary tumors reverted from an invasive type to a non-invasive type as well as potentially regaining sensitivity to hormonal therapy. Importantly, CX-5461 treatment also resulted in a marked reduction in the number of lung metastases. This suggests that treatment with CX-5461 may enhance hormone therapy responsiveness in patients where this kind of treatment doesn’t work anymore. We find this to be a remarkable breakthrough and we are currently pursuing a number of additional validation studies,” said Vincent.
It is known that some chemotherapy drugs inhibit ribosomal synthesis but don’t distinguish cancer cells from healthy cells. Other studies suggest that Curcumin, the active form of turmeric, also may inhibit ribosomal synthesis. If we can take away the cancer’s building blocks, we discourage growth.