A recent study from the University of Eastern Finland Institute of Biomedicine suggests that the SIX2 protein may be a cause of increased plasticity in prostate cancer cells, which can lead to treatment resistance. This is a significant challenge in the treatment of prostate cancer. The study was published in Nucleic Acids Research.Men and prostate cancer are the second leading cause of cancer death in Western countries. The growth of prostate cancer is fueled by androgens and can be managed with therapies that inhibit androgen receptors, particularly for aggressive or advanced prostate cancer. However, cancer cells can become resistant to these treatments, leading to castration-resistant prostate cancer.
One possible reason for treatment resistance is the flexibility of cancer cells: they can alter their level of differentiation and return to a stem cell-like state, which allows them to evade the effects of hormonal therapies. However, the factors that contribute to cell flexibility are not yet fully understood.The causes of treatment resistance in prostate cancer and the process of cancer cell development are not fully understood. Identifying these key factors is crucial in order to find new targets for therapies and potentially even a cure for these deadly types of cancer. Academy Research Fellow, Adjunct Professor (Docent) Kirsi Ketola of the University of Eastern Finland emphasizes the importance of this research.
The Ketola Lab’s recent study delved into potential factors that may contribute to treatment resistance, specifically the inhibition of the androgen receptor which could lead to the discovery of new genomic regions.nt resistance in prostate cancer.
DNA is packed into chromatin in cells and the openness of chromatin reflects active gene expression. The Ketola Lab conducted a study on chromatin openness in androgen-dependent prostate cancer cells treated with enzalutamide, an androgen receptor inhibitor used for prostate cancer treatment. The researchers discovered that after exposure to enzalutamide, there was a higher number of newly opened chromatin sites compared to newly closed sites. These newly opened sites were particularly found in DNA regions with SIX2 protein binding sites.The heightened activity of the protein SIX2 might be a factor in the increased adaptability of cells after undergoing drug treatment.
Basically, by blocking the function of the androgen receptor, the regulation of genes within cells is changed. This allows genes that are typically silenced to be expressed, and it also modifies the state of the cell.
SIX2 is vital for embryonic development, but it enhances the adaptability and aggressiveness of prostate cancer cells
The protein SIX2 is typically active during embryonic development, where it maintains cells as undifferentiated stem cells, preserving their ability to differentiate.The research discovered that the protein SIX2 has the ability to control how prostate cancer cells differentiate, even if they don’t have an androgen receptor. When cancer cells were exposed to enzalutamide, the activity of the SIX2 gene increased. Specifically, the SIX2 protein expression increased in cancer cells that did not express the androgen receptor.
Doctoral Researcher Noora Leppänen from the University of Eastern Finland stated, “On the other hand, silencing the SIX2 gene significantly reduced the aggressiveness of cancer cells resistant to hormonal therapies.” The stem cell- The state of cancer cells that do not have the androgen receptor, and their ability to move, invade, and spread to other parts of the body, was decreased significantly after the SIX2 gene was silenced. In experiments with zebrafish, it was also observed that there was less cell division and spread of cancer. This suggests that targeting the SIX2 protein could be a potential approach for developing drugs to treat or prevent the spread of hormone therapy-resistant types of cancer.
