A new protein linked to metastasis in pancreatic cancer says study

Pancreatic cancer is the No. 3 cause of cancer-related deaths in the United States, and only 12% of patients survive five years after being diagnosed. Severe pancreatic cancer is associated with metastasis, and it is this spread of secondary tumors that usually causes death, but little is known about the molecular mechanisms that drive metastasis.

In a study published in Advanced Science, researchers from the University of California, Davis showed that abnormal expression of the protein Engrailed-1 (EN1) promotes pancreatic cancer progression and metastasis in vitro and in mouse models. The team also found that elevated EN1 was associated with severe, metastatic pancreatic cancer in human patients, which suggests that EN1 might make a good target for pancreatic cancer therapies.

“We identified a novel epigenetic factor that can contribute to metastasis in pancreatic cancer, which is one of the most challenging cancers to treat,” said Chang-Il Hwang, an assistant professor in the UC Davis Department of Microbiology and Molecular Genetics and a senior author on the paper. “A better understanding of these mechanisms would allow us to identify potential targets and improve patient survival.”

One of these proteins, EN1, is essential for the survival of neurons during development and is not usually produced in adult pancreatic cells. EN1 has been shown to promote aggressive forms of breast cancer, and it is also associated with poor prognosis in other cancers, including glioblastoma and salivary gland adenoid cystic carcinoma, but its role in pancreatic cancer had not previously been described.

The researchers tested whether inhibiting EN1 or ramping up its expression impacted the growth and survival of pancreatic cancer “organoids” — three-dimensional clumps of lab-grown tissue. They found that, without EN1, pancreatic cancer cells were less likely to survive and divide, but adding extra EN1 increased the tumors’ survival. Furthermore, when the researchers genetically modified mouse pancreatic cancer cell lines so that they produced more EN1 than usual, the cells showed increased rates of cell invasion and migration, key features of metastasis.

Reference: Researchers identify protein linked to metastasis in pancreatic cancer; Advanced Science; DOI: 10.1002/advs.202308537