Scientists at Cold Spring Harbor Laboratory (CSHL) have made a groundbreaking discovery, uncovering the crucial role played by the protein SRSF1 in the development of pancreatic ductal adenocarcinoma (PDAC), a highly lethal form of pancreatic cancer. Elevated levels of SRSF1 were found to trigger inflammation and stimulate tumor growth, while restoring normal levels halted the progression of the disease. This significant finding has the potential to pave the way for new diagnostic techniques and innovative treatments for PDAC.
PDAC, the most prevalent type of pancreatic cancer, is known for its devastating prognosis. Over 90% of PDAC patients succumb to the disease within five years of diagnosis, primarily due to late detection when the cancer has already metastasized.
“By the time PDAC is identified, conventional treatments such as chemotherapy and surgery are often rendered less effective,” explains Professor Adrian Krainer of CSHL. “However, a comprehensive understanding of the underlying genetic mechanisms driving PDAC could lead to earlier diagnoses and novel therapeutic strategies.”
To delve into the role of RNA splicing—a genetic process—regarding pancreatic cancer, Krainer, along with CSHL Postdoc Ledong Wan, collaborated with Professor David Tuveson. RNA splicing assists DNA in conveying instructions to cells for protein production. The team focused their investigation on a splicing-regulator protein called SRSF1. Their research revealed that heightened levels of SRSF1 induce inflammation, specifically pancreatitis, thereby initiating the development of PDAC tumors.
While healthy pancreatic cells typically maintain a constant level of SRSF1, PDAC disrupts this equilibrium, causing a surge in SRSF1 levels. Krainer remarks, “Cancer tends to exploit mechanisms that keep SRSF1 levels stable.”
Numerous genes, RNAs, and proteins work in tandem within cells to regulate SRSF1 levels. Unfortunately, these processes can be disrupted, leading to pancreatic inflammation and accelerating PDAC progression.
Krainer notes, “The effect is striking. We observed that patients with elevated SRSF1 expression in their tumors experienced worse outcomes. Hence, we embarked on uncovering the extent to which SRSF1 contributes to PDAC.”
Through experiments conducted on mice and organoids (miniature tumor models), the team confirmed that increased SRSF1 levels are crucial for PDAC growth. Importantly, when SRSF1 levels were restored to normal, the organoids ceased to grow. Given that SRSF1 serves essential functions in healthy tissue, targeting it directly may not be ideal as a drug therapy. However, specific splicing changes facilitated by SRSF1 could be viable targets for intervention. Krainer emphasizes that more research is needed to fully comprehend the intricacies of PDAC.
“We are highly enthusiastic about these findings,” he states. “Yet, PDAC is a complex and challenging malignancy. Our goal is to provide actionable insights for future treatments. The work spearheaded by Ledong is just the beginning.”
Krainer and Wan’s collaboration with the Tuveson lab forms part of a broader initiative to explore pancreatic and breast cancers. This endeavor also involves Professors David Spector and Christopher Vakoc from CSHL.
Tuveson, the director of the CSHL Cancer Center, praises the Krainer lab’s paradigm-shifting work, which has enhanced understanding across various cancer types. He comments, “Dr. Wan’s research has unveiled an exciting avenue for comprehending pancreatic cancer, reaffirming the significance of fundamental biological research in improving human health.”
Reference: “Splicing Factor SRSF1 Promotes Pancreatitis and KRASG12D-Mediated Pancreatic Cancer” by Ledong Wan, Kuang-Ting Lin, Mohammad Alinoor Rahman, Yuma Ishigami, Zhikai Wang, Mads A. Jensen, John E. Wilkinson, Youngkyu Park, David A. Tuveson, and Adrian R. Krainer, 26 April 2023, Cancer Discovery. DOI: 10.1158/2159-8290.CD-22-1013
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Frequently Asked Questions (FAQs) about Pancreatic cancer research
What is the role of the protein SRSF1 in pancreatic cancer?
The protein SRSF1 plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). Elevated levels of SRSF1 can trigger inflammation and stimulate tumor growth, while restoring normal levels can halt the progression of the disease.
How common is pancreatic ductal adenocarcinoma (PDAC)?
PDAC is the most common form of pancreatic cancer. Unfortunately, it is also one of the deadliest. Over 90% of PDAC patients die within five years of diagnosis.
Can understanding the genetic mechanisms of PDAC lead to earlier diagnoses and new treatments?
Yes, understanding the underlying genetic mechanisms of PDAC could potentially lead to earlier diagnoses and the development of new types of therapies. By comprehending the genetic factors involved, it may be possible to identify PDAC at earlier stages when treatments can be more effective.
What are some potential implications of this research?
The discovery of the role of SRSF1 in PDAC opens up new avenues for diagnostic methods and treatments. It may pave the way for the development of innovative therapies targeting specific splicing changes facilitated by SRSF1. Additionally, this research highlights the importance of basic biological research in improving human health and provides valuable insights into the complexity of PDAC.
Is there ongoing research in this area?
Yes, the research on pancreatic cancer, including the role of SRSF1, is an active area of study. Scientists are continually exploring the mechanisms of PDAC and seeking further advancements in diagnostics and treatments.
More about Pancreatic cancer research
- Cold Spring Harbor Laboratory: https://www.cshl.edu/
- Cancer Discovery Journal: https://cancerdiscovery.aacrjournals.org/
- PubMed: https://pubmed.ncbi.nlm.nih.gov/
- American Cancer Society: https://www.cancer.org/
- National Cancer Institute: https://www.cancer.gov/
