Hebrew University research published in the prestigious Nature journal identifies the cause of cancer spread, making disease fatal, and offers possible ways to block it and prolong life
Researchers compared approximately 400 non-metastatic pancreatic tumor growths to metastatic growth cells, and found that changes in RNA molecule processing within the cell, rather than genetic changes in the DNA, were responsible for the growths becoming metastatic.
Metastatic growths are the main cause of death from pancreatic cancer, which has very few ways of treatment and is therefore considered the most lethal form of cancer.
The study was led by doctoral student Amina Jabara from the research team of Prof. Rotem Karni, an expert in molecular cancer biology at the Faculty of Medicine at the Hebrew University.
The researchers found that a central protein that controls RNA processing, called RBFOX2, undergoes degradation and disappears in metastatic cells. The disappearance of RBFOX2 causes hundreds of genes to produce RNA and proteins in a different manner, contributing to the invasiveness of the cells.
Researchers showed that reintroducing RBFOX2 to metastatic cells inhibits the formation of metastases, while its suppression stimulates the formation of pancreatic cancer metastases.
The disappearance of RBFOX2 specifically affects a group of genes that control the organization of the cell cytoskeleton, which is important for the mobility and invasive ability of the cells.
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The researchers demonstrated that by using a drug that inhibits the activity of this group of genes, which is currently used to treat organ transplant patients, the formation of pancreatic cancer metastases can be delayed.
Additionally, by genetically intervening in the processing of RNA in the RBFOX2’s target cells, researchers were able to eliminate the cancer cells’ invasive ability. When such cells were taken from the bodies of patients and translated into mice, no metastases occured.
According to Prof. Karni, “The study’s findings for the first time explain the molecular basis (which isn’t genetic) for the transformation of cancer cells into invasive pancreatic cells and propose two ways of treatment: a known drug that inhibits a pathway affected by RBFOX2, or RNA-based therapy that intervenes in the RNA process affected by RBFOX2 to treat invasive pancreatic cancer.”
The research was conducted in collaboration with researchers and physicians from the Sheba Medical Center and Bar-Ilan University in Israel, U.S.-based Cornell University, Canada’s Toronto University, and the Cold Spring Harbor Labs research laboratory.