In a new study, researchers from Nottingham Trent University in the United Kingdom have determined how a specific enzyme plays a key role in making prostate cancer more aggressive and harder to treat. They found that the enzyme, called transglutaminase 2 (TG2), which is abundant in many cells of the body, is responsible for driving the process that leads to the progression and spread of prostate cancer. The findings were recently published in the journal Cell Death & Disease in a paper titled "Canonical and truncated transglutaminase-2 regulates mucin-1 expression and androgen independency in prostate cancer cell lines".
Early prostate cancer cells require androgens to grow, but as they progress, they become androgen-independent and therefore more difficult to treat with current therapies.
Until then, it was unclear how this process occurred, but after conducting a series of tests, these authors found that a mutant form of TG2 is overproduced in prostate cancer and remains trapped in the nucleus of prostate cancer cells. There, it limits the level of androgen response, making prostate cancer cells more aggressive and androgen-independent, and increases the expression of the protein "mucin-1", which is known to be responsible for the growth and spread of cancer. This new study also found that mucin-1 forms a mucus barrier on the cell surface that protects cancer cells.
To further support this study, these authors analyzed biopsies from prostate cancer patients and found increased levels of TG2. Although it can exert a protective effect in vivo, TG2 is associated with a variety of human diseases, including neurodegenerative disorders such as dementia and organ fibrosis. These authors propose that controlling the activity of TG2 and mucin-1 may provide a new therapeutic option for the treatment of aggressive prostate cancer.
Prostate cancer is the most common cancer in men in the UK, with more than 52,000 people diagnosed each year. Dr. Elisabetta Verderio Edwards, corresponding author of the paper and lead scientist at Nottingham Trent University's School of Science and Technology, said, "We wanted to explore why some prostate cancer cells become androgen-independent and therefore more aggressive and harder to treat."
Image from Cell Death & Disease, 2023, doi:10.1038/s41419-023-05818-9
TG2 is a multifunctional protein present in all tissues and involved in a variety of processes," she said. We have now deepened our understanding of its key role in this aggressive disease in prostate cancer patients. It is very important to understand this pathway. This process plays a key role in the ability of cancer to evade treatment and therefore deserves further study in terms of potential future treatments and therapies."
Dr. Adeola Atobatele, first author of the paper, said, "This discovery opens an important avenue for understanding other key mechanisms utilized by prostate cancer cells to evade critical regulatory pathways."
Last year, researchers at Nottingham Trent University revealed how tiny "nano-shuttles" transport TG2 around the brain, where it continues to play a role in neuronal activity
