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.
Micrograph showing a pancreatic tumor with experimentally depleted levels of En1, which reduces metastatic activity. Image Credit: Jihao Xu
In a study published Dec. 18 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.”
Uncovering a main actor in pancreatic metastasis
Metastasis is an important component of pancreatic cancer progression, but researchers have not been able to identify genetic mutations responsible for it. For this reason, Hwang thought that nongenetic factors, such as epigenetic changes or altered protein production, might be at play. His team previously identified