Hebrew University Researchers Identify How Pancreatic Cancer Cells Metastasize and Become Fatal
Discovery Could Lead to New Pancreatic Cancer Treatments
NEW YORK - March 22, 2023 -- A team of researchers led by the Hebrew University in Jerusalem (HU) have identified the mechanism that causes tumors to metastasize in pancreatic ductal adenocarcinoma (PDA). The study was published today in Nature.
PDA is an aggressive, malignant disease of the exocrine pancreas with a five-year survival rate of less than 5%. It is characterized by aggressive local invasion and metastatic spread.
The multinational study was led by doctoral student Amina Jabara of Prof. Rotem Karni’s research lab at Hebrew University’s Faculty of Medicine in collaboration with Sheba Medical Center and Bar Ilan University in Israel as well as, Toronto University, Cornell University, and Cold Spring Harbor Labs in New York. Video of Karni and Jabara.
The researchers evaluated approximately 400 PDA tumors, both non-metastatic and metastatic. They found that RBFOX2, a central protein that controls RNA processing, is degraded and present in much lower levels in metastases. These findings support the role of RBFOX2 as a potent metastatic suppressor in PDA.
"For the first time, these research findings explain the molecular (non-genetic) basis by which pancreatic cancer cells become metastatic," Karni says. "In addition, these findings offer two possible options for treatment of metastatic pancreatic cancer: either a known drug that inhibits a process affected by RBFOX2, or an RNA-based therapy that intervenes in the processing of specific RBFOX2-affected RNAs.”
The disappearance of RBFOX2 specifically affects a group of genes that control the organization of the cell skeleton and are important for the cells' motility and invasive ability. The researchers found that, by using a drug that currently treats organ transplant patients and inhibits this gene group activity, it is possible to delay pancreatic cancer metastases.
Through genetic intervention in RNA processing of target RBFOX2 genes, researchers also showed it is possible to cancel the metastatic ability of pancreatic cancer cells taken from patients so they cannot form metastases when transplanted into mice.
“Our findings demonstrate that the disappearance of RBFOX2 causes hundreds of genes to produce RNA and proteins in a different way, which contributes to the invasion of the cells,” says Karni. “We found that restoring RBFOX2 to metastatic cells inhibits the formation of metastases, while the elimination of RBFOX2 stimulates the formation of pancreatic cancer metastases.”
The study was funded by grants from: Alex U. Soyka Pancreatic Cancer Research grant (CFHU), Israel Cancer Association (ICA) - 20220038, Israel Science Foundation (ISF) - 1510/17, United States - Israel Binational Science Foundation (BSF) - 2021108 [R. Karni] and Israel Ministry of Science, Zvi Yanai Ph.D., and post-doctoral fellowship program for outstanding minority students [A. Jbara].
About the Hebrew University of Jerusalem
The Hebrew University of Jerusalem is Israel's leading academic and research institution. Serving some 24,000 students from 80 countries, it produces a third of Israel’s civilian research and is ranked 12th worldwide in biotechnology patent filings and commercial development. Faculty and alumni of the Hebrew University have won eight Nobel Prizes and a Fields Medal. For more information about the Hebrew University, please visit http://new.huji.ac.il/en.
About American Friends of the Hebrew University
American Friends of the Hebrew University (AFHU) is a national, not-for-profit organization based in the United States. AFHU is headquartered in New York and has seven regional offices working in close partnership with the Hebrew University of Jerusalem. AFHU provides supporters, Hebrew University alumni, and the public with stimulating programs and events, and organizes missions to Israel. The organization’s activities support scholarly and scientific achievement at HU, create scholarships, fund new facilities, and assist the university’s efforts to recruit outstanding new faculty.
For more information, please visit http://www.afhu.org.
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