Pancreatic cancer ranks as the third leading cause of cancer-related deaths in the United States. With only a 12% survival rate five years after diagnosis, it is clear that finding effective treatments for this aggressive disease is crucial. Metastasis, the spread of secondary tumors, is a major factor in the severity and poor prognosis of pancreatic cancer. However, the molecular mechanisms driving metastasis have been largely unknown. In a groundbreaking study published in Advanced Science, scientists from the University of California, Davis reveal that abnormal expression of a protein called Engrailed-1 (EN1) plays a significant role in promoting pancreatic cancer progression and metastasis.
The research team conducted in vitro experiments and mouse models to demonstrate the contribution of EN1 in pancreatic cancer metastasis. They discovered that elevated levels of EN1 were associated with severe metastatic cancer in human patients, revealing its potential as a viable target for future pancreatic cancer therapies. According to Chang-Il Hwang, an assistant professor in the UC Davis Department of Microbiology and Molecular Genetics and senior author of the study, “We identified a novel epigenetic factor that can contribute to metastasis in pancreatic cancer, which is one of the most challenging cancers to treat.” This newfound understanding of the molecular mechanisms underlying pancreatic cancer metastasis could lead to the identification of potential targets and improved patient survival rates.
While researchers have previously struggled to identify genetic mutations responsible for metastasis in pancreatic cancer, Hwang and his team suspected that nongenetic factors, such as epigenetic changes or altered protein production, might be at play. In previous studies, the team had identified several transcription factors, including EN1, that were elevated in metastatic pancreatic tumors compared to primary tumors. EN1 is typically produced during the development of neurons and is not commonly found in adult pancreatic cells. It has been linked to aggressive forms of breast cancer, as well as poor prognosis in other cancer types such as glioblastoma and salivary gland adenoid cystic carcinoma. However, its role in pancreatic cancer had not been previously described.
To investigate the impact of EN1 on pancreatic cancer, the researchers conducted experiments using pancreatic cancer organoids, which are three-dimensional clumps of lab-grown tissue. They found that when EN1 was inhibited, pancreatic cancer cells were less likely to survive and reproduce. Conversely, when EN1 expression was increased, tumor cells exhibited enhanced survival rates. The researchers genetically modified mouse pancreatic cancer cell lines to produce higher levels of EN1, resulting in increased cell invasion and migration, both characteristic features of metastasis.
Jihao (Reno) Xu, a doctoral candidate in the Biochemistry, Molecular, Cellular and Development Biology graduate group and first author of the study, emphasizes the importance of EN1 in the aggressiveness of pancreatic cancer, stating, “It’s very clear that EN1 is a really important factor behind the aggressiveness of pancreatic cancer. When we take the tumor cells and make them overexpress EN1, they become more metastatic and aggressive, and when we knock it down, they become less metastatic.”
This groundbreaking study not only sheds light on the role of EN1 in pancreatic cancer metastasis but also presents the possibility of targeting EN1 as a therapeutic approach for the treatment of this deadly disease. As scientists continue to unravel the molecular mechanisms governing pancreatic cancer progression, there is hope for the development of more effective therapies and improved patient outcomes.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
