Breast cancer is a prevalent form of cancer among women, originating from epithelial cells in the mammary gland. These cells are responsible for milk production during and after pregnancy. A team of researchers from Friedrich Schiller University Jena, the University in Shenzhen, and Jena University Hospital have delved into the process of cell specialization, revealing a molecular mechanism that plays a crucial role in cancer development. These findings could potentially lead to the development of innovative diagnostic procedures and treatment methods for breast cancer.
Cell differentiation, also known as cell specialization, occurs when cells undertake different tasks. During lactogenesis, which is the process that allows mammary glands to produce milk due to hormonal triggers, the relevant cells multiply. This multiplication is facilitated by ribosomes, which produce the necessary proteins. Ribosomal RNA (rRNA) is a fundamental component of ribosomes.
When more proteins are required, the demand for rRNA increases, leading to its synthesis being augmented in the cell nucleus. At the end of lactogenesis, the specialized cells cease growth and reduce rRNA synthesis. This regulatory process occurs at the epigenetic level, wherein the packaging of DNA is altered by a specific RNA.
The researchers identified a long, non-coding RNA named PAPAS, which was previously discovered a few years ago. PAPAS acts on DNA packaging and diminishes rRNA production. Its influence determines whether active regions of DNA are copied into RNA. If an abundance of ribosomes, proteins, and consequently rRNA is needed, the synthesis of PAPAS is reduced. Conversely, an increase in PAPAS levels signals a halt to this process.
The experts also discovered that PAPAS not only plays a significant role in cell proliferation but also in specialization. When PAPAS was disabled through gene manipulation, cells were no longer able to develop into milk-producing cells. The researchers also found that cancer cells increase synthesis of rRNA as they multiply rapidly and require a substantial amount of proteins and ribosomes. Therefore, the regulatory mechanism observed in breast cancer development is evidently interconnected.
When PAPAS synthesis was reduced, and cell specialization was switched off, the cells began to exhibit characteristics of cancer cells. Conversely, the researchers demonstrated in cell cultures and mice that elevated levels of PAPAS reduced tumor growth and the spread of metastases.
The question remains: how do cancer cells suppress PAPAS production and subsequently enhance rRNA synthesis? The researchers discovered a mechanism in which the production of PAPAS requires a molecular signal at the start of the PAPAS gene. This signaling structure is regulated by specific proteins, which can either activate or inhibit the structure. Breast cancer cells were found to exhibit elevated levels of these proteins, with greater aggression associated with higher quantities.
The research results hold promise for Dr. Holger Bierhoff, who sees two significant implications. Firstly, PAPAS could serve as an interesting marker for assessing the aggressiveness of breast tumors and potentially be used as a diagnostic tool. Secondly, the researchers are already working on RNA therapy for cancer treatment. By understanding the mechanism by which PAPAS regulates rRNA synthesis and identifying the required region of the RNA, they aim to produce this specific part of PAPAS artificially, package it in nanoparticles, and introduce it into cancer cells to restore its functionality. This approach would reduce rRNA synthesis, hindering cancer proliferation. In essence, this strategy is similar to mRNA vaccines, such as those developed for COVID-19, albeit employing regulatory RNA instead of protein-coding RNA.
1. Source: Coherent Market Insights, Public sources, Desk research
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