Cancer Culprit: Scientists Uncover the Elusive ‘Mutant’ Enabling Prostate Cancer to Elude Treatment

In a remarkable scientific discovery, researchers have unraveled the intricate role of a specific substance that fuels the spread and resistance of prostate cancer, potentially opening new doors for treating this aggressive form of the disease.

The team at Nottingham Trent University has identified “transglutaminase 2” (TG2), a protein abundantly present in various cells throughout the body, as the driving force behind a process that leads to the progression and metastasis of prostate cancer.

Prostate cancer is the most prevalent cancer among men in the UK, with over 52,000 new cases diagnosed annually. In its early stages, prostate cancer cells rely on the hormone androgen for growth. However, as the disease advances, these cells can become androgen-independent, rendering them more challenging to treat with current therapies.

Until now, the mechanisms behind this transformation have remained elusive. “This finding has opened a significant pathway for understanding other key mechanisms prostate cancer cells utilize to evade key regulatory pathways,” explains Dr. Adeola Atobatele, a scientist involved in the study.

The groundbreaking research reveals that a mutated form of TG2 is overproduced in prostate cancer cells, where it becomes trapped inside the cell nucleus. Within this confined space, TG2 suppresses androgen response, fueling the aggressiveness and androgen-independence of the cancer cells. Furthermore, it stimulates the production of mucin-1, a protein known for promoting cancer growth and metastasis.

The study also highlighted that mucin-1 forms a protective barrier, akin to mucous, on the surfaces of cancer cells, shielding them from the body’s defenses.

Through analyzing prostate cancer biopsies, researchers observed elevated levels of TG2, providing strong evidence of its significant role in the disease.

Armed with these findings, the research team proposes that controlling the activity of TG2 and mucin-1 could present a promising therapeutic avenue for combating aggressive prostate cancer.

Dr. Elisabetta Verderio Edwards, the lead scientist from Nottingham Trent University’s School of Science and Technology, explains, “We sought to uncover the reasons why certain cancer cells become androgen-independent, leading to increased aggressiveness and treatment resistance. Transglutaminase is a multifunctional protein involved in various biological processes. Our understanding of its pivotal role in the progression of aggressive prostate cancer has deepened.”

Recognizing the importance of this pathway, Dr. Verderio Edwards emphasizes the need for further investigation to explore potential future treatments and therapies targeting this process that enables cancer cells to evade treatment.

The groundbreaking study, conducted in collaboration with the Polyclinic Hospital University (University of Messina) in Italy, has been published in the esteemed journal Cell Death and Disease. This remarkable breakthrough paves the way for future advancements in the fight against prostate cancer and offers hope for improved treatment strategies that can tackle its aggressive nature head-on.