Aditya Dutta, of the University of Delaware, and collaborators are investigating the NKX3.1 gene and its role in prostate cancer, the most common cancer and the second leading cause of cancer death among men in the United States.
In prostate biology, NKX3.1 is large. The gene regulates everything: development, maintenance, initiation and progression of the disease.
In a new research article published in Discovery of cancer, the researchers found that under stress, NKX3.1 shifts to the mitochondria—The power of the cell — in order to protect it prostate cancer. Mitochondria play a key role in stress responses.
“Mitochondria are like the coal mine canary,” said Dutta, an UD assistant professor with appointments in both the Department of Animal and Food Sciences and the Department of Biological Sciences. “They act as stress sensors and drive the cell’s response to stress.”
Most patients diagnosed with prostate cancer they are placed under active surveillance. Stopped follow-up determines exactly when the cancer will become aggressive. The results of this study are promising for these patients. Microscopic histological analysis of NKX3.1 will allow for a precision prevention approach, helping patients determine the risk of progression to an aggressive disease.
“The role of NKX3.1 in prostate cancer has been known for more than two decades; however, its role was limited to its function in the cell nucleus,” Dutta said. “Our analysis of NKX3.1 in animal models and in human prostate specimens indicated the presence of the gene outside the nucleus, specifically in mitochondria.”
NKX3.1 and prostate cancer risk
NKX3.1 is a major regulator that suffers functional loss in up to 80% of early-stage prostate cancers. Analyzes show that NKX3.1 loss is the start-up event in the evolution of prostate cancer. In addition, the aggressiveness of prostate cancer in African American men is related to reduced levels of NKX3.1. The researchers identified the lack of mitochondrial function NKX3.1 in two mutations associated with an increased risk of aggressive prostate cancer, highlighting the potential use of the non-nuclear localization NKX3.1 as a risk assessment tool in the prostate cancer.
“This means we can look for NKX3.1 outside the core and, if in fact it is out, your chances of developing aggressive diseases increase significantly,” Dutta said. “Need treatment immediately.”
Mitochondria: friend or foe of the tumor?
Mitochondria play a unique role in tumors. In normal cells, mitochondrial energy production is usually related to nutrient uptake. However, in cancer cells this is not the case; they redirect nutrients to cause more DNA to multiply rapidly. Cancer cells need to grow fast. Growth needs energy. Therefore, cancer cells participate in a good balance, obtaining the right amount of energy for growth.
“It reminds you of a juggler who makes sure the pines never fall and the show goes on,” Dutta said. “NKX3.1 moves to mitochondria to ensure optimal energy production and causes spectacle, causing oxidative stress prostate initiation and progression of cancer in this case, to the end “.
Alexandros Papachristodoulou et al, NKX3.1 localization in mitochondria suppresses initiation of prostate cancer, Discovery of cancer (2021). DOI: 10.1158 / 2159-8290.CD-20-1765
University of Delaware
Citation: Precision Prevention of Prostate Cancer (2021, June 7), retrieved June 7, 2021 at https://medicalxpress.com/news/2021-06-precision-prostate-cancer.html
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