In a new study, researchers from Nottingham Trent University in the UK identified how a specific enzyme plays a key role in making prostate cancer more invasive and difficult to treat. They found that this enzyme, called transglutaminase 2 (TG2), which is abundant in many cells of the body, is responsible for driving the process leading to the progression and spread of prostate cancer. The relevant research results have recently been published in the journal Cell Death & Disease, with the title “Canonical and truncated transglutaminase-2 regular mucin-1 expression and androgen dependence in prostate cancer cell lines”.
Early prostate cancer cells require androgens to grow, but as they develop, they become independent of androgens, making it more difficult to treat with current treatment methods.
Prior to this, it was not clear how this process occurred, but after conducting a series of tests, these authors found that a mutated form of TG2 was overproduced in prostate cancer and had been trapped in the nucleus of prostate cancer cells. There, it limits the level of androgen response, making prostate cancer cells more invasive and androgen-independent, and increasing the expression of the protein “mucin-1”, which is known to be responsible for cancer growth and spread. This new study also found that mucin-1 forms a mucous barrier on the cell surface to protect cancer cells.
(Adeola Grace Atobatele et al. 2023)
To further support this study, these authors analyzed the living tissues of prostate cancer patients and found an increase in TG2 levels. Although it can play a protective role in the body, TG2 is associated with a variety of human diseases, including neurodegenerative diseases, such as dementia and organ fibrosis. These authors suggest that controlling the activity of TG2 and mucin-1 may provide a new treatment option for invasive prostate cancer.
In the UK, prostate cancer is the most common cancer among men, with over 52000 people diagnosed each year. Dr. Elisabetta Verderio Edwards, the corresponding author of the paper and the chief scientist of the School of Science and Technology of Nottingham Trent University, said, “We want to explore why some prostate cancer cells become independent of androgen, which makes them more invasive and difficult to treat.”
She said, “TG2 is a multifunctional protein present in all tissues and involved in various processes. We have now deepened our understanding of its key role in this invasive disease in prostate cancer patients. Understanding this pathway is crucial. This process plays a crucial role in the ability of cancer to evade treatment, and therefore deserves further research in potential future treatments and therapies.”
Dr. Adeola Atobatele, the first author of the paper, said, “This discovery opens up an important pathway for understanding other key mechanisms utilized by prostate cancer cells to evade key regulatory pathways.”
Last year, researchers from Nottingham Trent University revealed how the tiny “nano shuttle” transported TG2 around the brain, where it continued to play a role in neuronal activity.
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Reference
Adeola Grace Atobatele et al. Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines. Cell Death & Disease, 2023, doi:10.1038/s41419-023-05818-9.