Scientist have found a potential target for anti-lung cancer drugs, by identifying a gene called 14-3-3zeta, which when silenced, doesn't allow lung cancer cells to survive.
The study was led by Haian Fu, PhD, professor of pharmacology, hematology & oncology at Emory University School of Medicine and Emory Winship Cancer Institute.
AdvertisementZenggang Li, PhD, a postdoctoral fellow in Dr. Fu's laboratory and the first author of the study, said that though lung cancer kills more Americans per year as compared to any other type of malignancy, the treatment options are still very limited.
"The recent trend towards targeted therapies requires us to understand the altered signaling pathways in the cell that allow cancer to develop," said Dr. Fu.
He added: "If you think about genes that are dysregulated in cancer as drivers or passengers, we want to find the drivers and then, aim for these drivers during drug discovery."
The research team focused specifically on the gene 14-3-3zeta as it is activated in many lung tumors. Also, according to Dr. Fu, the survival of lung cancer patients is worse if the gene is overtly active in their tumors as shown by a recent research elsewhere.
The 14-3-3 genes are found in mammals, plants and fungi. However, there are seven types of the same in the human body and each is represented by a Greek letter.
The researchers describe the proteins encoded by these genes as adaptors clamping onto other proteins. This clamping function is governed by whether the target protein is phosphorylated, a chemical switch that regulates processes such as cell division, growth, or death.
"We knew that 14-3-3 is important in controlling EGFR (epidermal growth factor receptor) signaling, which is a main pathway driving lung cancer," said Dr. Fu.
He also added that a couple of drugs that were launched recently were found to be effective against lung cancer target EGFR.
The researchers used a technique known as RNA interference to selectively silence the 14-3-3zeta gene.
It was found that by turning off 14-3-3zeta, lung cancer cells turn out to be less able to form new tumor colonies in a laboratory test.
One of the most important properties of cancer cells is their ability to grow and survive without touching other cells or the polymers that connect them.
It was found that the cells with silenced 14-3-3zeta do not grow more slowly but the cells were susceptible to anoikis (Greek for homelessness) which is a form of cell death that happens when non-cancerous cells accustomed to growing in layers find themselves alone.
In further experiments it was shown that 14-3-3zeta regulates a set of proteins called the Bcl2 family controlling programmed cell death, and the balance within the family is disturbed by its absence.
"You can see how control of anoikis means 14-3-3zeta could play a critical role in cancer invasion and metastasis. The mechanistic question we still haven't answered is: what makes zeta unique so that it can't be replaced by the others," said Dr. Fu.
Dr. Fu indicated that as 14-3-3zeta is also activated in other forms of cancer such as breast and oral, the results can also find implications beyond lung cancer.
The study was published recently in the Proceedings of the National Academy of Sciences (PNAS).
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