This killer protein causes pancreatic cancer

Mouse pancreas cells with high levels of the protein SRSF1; CSHL Professor Adrian Krainer found that mice with high levels of SRFS1 tend to exhibit intraepithelial neoplasia—a known precursor to the most common form of pancreatic cancer.
Credit: Krainer lab/Cold Spring Harbor Laboratory

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. It’s also one of the deadliest. More than 90% of PDAC patients die within five years of diagnosis. Usually, by the time the cancer is identified, it has already spread.

“PDAC is often found too late for treatments like chemotherapy and surgery to be very effective,” Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer says. “But if we can clearly understand the underlying genetic mechanisms of PDAC, this might lead to earlier diagnoses and new types of therapies.”

Krainer and CSHL Postdoc Ledong Wan partnered with CSHL Professor David Tuveson to explore the role of a genetic process called RNA splicing in pancreatic cancer. RNA splicing helps DNA deliver instructions to cells for protein production. The team zeroed in on a splicing-regulator protein called SRSF1. They found that high levels of SRSF1 cause inflammation, or pancreatitis. This jumpstarts PDAC tumor development.

“Cells have several processes to keep SRSF1 levels constant,” says Krainer. “But cancer tends to find a way to overcome these checks and balances.”

Several genes, RNAs, and proteins work together in cells to keep SRSF1 levels steady. But sometimes, the process gets disrupted. In the pancreas, this triggers pancreatitis and accelerates PDAC.

“It’s a very pronounced effect,” Krainer explains. “We could see that patients whose tumors express higher levels of SRSF1 have worse outcomes. So, we set out to explore to what extent SRSF1 contributes to PDAC.”

The team found that higher levels of SRSF1 are essential for PDAC growth in mice and organoids—small versions of tumors. Furthermore, when SRSF1 returned to normal levels, the organoids stopped growing. SRSF1 is important in healthy tissue, so it may not be an ideal drug target by itself. However, some of the splicing changes it promotes could be targeted instead. Krainer says there is still more work to be done.

“We’re excited by these developments,” he says. “But PDAC is a difficult and complicated malignancy. We’re hoping to provide actionable information for future treatments. This work spearheaded by Ledong is just the tip of the iceberg.”

Krainer and Wan’s collaboration with the Tuveson lab is part of a broader effort to explore pancreas and breast cancer. The initiative also includes CSHL Professors David Spector and Christopher Vakoc.

“The Krainer lab’s paradigm-shifting work has led to a deeper understanding of many types of cancer,” says Tuveson, director of the CSHL Cancer Center. “Dr. Wan’s research reveals an exciting new avenue to understand pancreatic cancer. It reaffirms the importance of basic biological research for the improvement of human health.”

Journal: Cancer Discovery
DOI: 10.1158/2159-8290.CD-22-1013
Article Title: Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer
Article Publication Date: 26-Apr-2023

Media Contact

Samuel Diamond
Cold Spring Harbor Laboratory
diamond@cshl.edu
Office: 5163675055

www.cshl.edu

Media Contact

Samuel Diamond
Cold Spring Harbor Laboratory

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

The last missing piece of silicon photonics

International research team presents first electrically pumped continuous-wave semiconductor laser suitable for seamless silicon integration. Scientists from Forschungszentrum Jülich, FZJ, the University of Stuttgart, and the Leibniz Institute for High…

Space-time crystals, an important step toward new optical materials

KIT scientists design tailored materials for optical information processing. Photonic space-time crystals are materials that could increase the performance and efficiency of wireless communication or laser technologies. They feature a…

Quasiparticle loss in extreme quantum materials

A new study by Rice University physicist Qimiao Si unravels the enigmatic behaviors of quantum critical metals — materials that defy conventional physics at low temperatures. Published in Nature Physics…