Molecular “Detector” Developed to Identify and Kill Potential Cancer Cells

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Highlights:

• Key tumor-suppressor gene TP53 codes for the p53 protein that plays a role in anticancer function and apoptosis
• Mutations in TP53 gene severely compromise tumor suppression
• Damaged TP53 genes can now be detected by a genetic sensor that then goes ahead and kills the potential cancer cells.

Scientists and medical faculty working across institutions at Dresden, Germany have developed a sensor which detects mutations in tumor-suppressor gene TP53 and then goes on to kill potential cancerous cells. The research study has been published in Nature Communications

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Sensor to detect and kill potential cancer cells

TP53 is a key tumor-suppressor gene. A mutation in TP53 gene can prevent the gene from taking action on potentially cancerous cells. TP53 works by producing protein p53 which determines if DNA-damaged cells can be repaired or not. By regulating cell division and cell apoptosis (cell death), p53 plays a major role in preventing cancers. p53 is often referred to as “guardian of the genome.”

However, a mutation in this key gene TP53 leads to gaps in the production of p53 protein. This in turn leads to unnatural cell division and cancerous tumors in the absence of cell regulation and apoptosis.

In mouse models, the researchers found that the loss of p53 predisposed the mice to a range of tumors. It is also established that 50% of all human cancers are due to mutations in the TP53 gene. Researchers have been trying to target p53 pathways to combat cancer. There has been some progress in the identification of drugs which restore the function of damaged TP53 gene; however, the clinical responses have not been satisfactory.

Research advances in synthetic biology have great therapeutic potential. The researchers in this study designed and built a genetic p53 device which could detect the p53 status in human cells. This sensor is capable of detecting any changes in p53 function thereby accelerating the time frame of early-state cancer detection. The sensor was tested in primary human cell lines in vitro and mouse models in vivo.

According to Professor Frank Buchholz, the research study is extremely significant for early-stage cancer detection and prevention. The study’s results have indicated that cells with p53 mutations can be quickly detected and eliminated from the body thereby preventing the development of cancerous tumors. The research study also has immense potential wherein the sensor can be used to detect other mutated genes in the body causing other diseases.

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Overview of TP53 Gene and p53 Protein 

The TP53 gene has instructions to code for the tumor-suppressor protein p53. p53 regulates cell division and prevents the unnatural division and multiplication of cells leading to cancerous tumors. p53 protein is located in the nucleus of cells all over the body where it has a binding affinity to DNA. If the DNA becomes damaged due to epigenetic conditions, p53’s role is to determine if the damaged DNA will be repaired or the cell undergoes apoptosis or cell death. p53 has a major role in signaling the repair of DNA or signaling cell death to prevent cancers.

References:

1. Mircetic, Jovan, Antje Dietrich, Maciej Paszkowski-Rogacz, Mechthild Krause, and Frank Buchholz. "Development of a genetic sensor that eliminates p53 deficient cells." Nature Communications 8, no. 1 (2017): 1463. doi:10.1038/s41467-017-01688-w
2. TP53 gene - (https://ghr.nlm.nih.gov/gene/TP53)

Source-Medindia