Two sets of proteins have been identified as working together to fend off the growth of pancreatic cancer.
Scientists at VCU Massey Cancer Center discovered the relationship, which could provide pivotal information for the development of novel therapies in treating what is currently an incurable disease.
The vast majority of all pancreatic tumors are attributed to Pancreatic ductal adenocarcinoma (PDAC), the fourth-leading cause of cancer-related deaths worldwide. Patients are usually diagnosed at an advanced stage when the disease is already inoperable and there are no effective therapies.
New research published in the Journal of Cell Biology was led by Dr. Azeddine Atfi, leader of the Cancer Biology research program who holds the Mary Anderson Harrison Distinguished Professorship in Cancer Research at Massey. Atfi discovered that the simultaneous activation of two gene-regulating proteins, Prdm16 and Smad4, is associated with a cutback in pancreatic cancer progression.
“Our study sheds light on a previously uncharacterized interplay between Smad4 and Prdm16, which appears to dictate the growth trajectory of pancreatic cancer, that could ultimately pave the way for innovative therapeutic breakthroughs to curb this deadly disease,” Atfi, who is also a professor in the Department of Biochemistry and Molecular Biology at the VCU School of Medicine, said.
Smad4 has previously been connected to cancer growth in PDAC cells when absent, while Prdm16 controls a variety of essential cellular processes, including the construction of tissues and organs. Observation of the protein was first made in leukemia, and previous research indicated it might function as a tumor suppressor.
“Think of Smad4 as a movie director telling Prdm16 how to fulfill the role of a cancer fighter. Without Smad4 as the director, Prdm16 starts to play the part of a cancer supporter,” Atfi said. “Our findings point to a previously unidentified mechanism that orchestrates the antitumor role of Prdm16, and further shed new insights into the molecular cause of pancreatic cancer.”
More research is necessary to confirm if Prdm16 elicits anti-tumor activity at early stages, and, if so, if it directly affects cancer cell growth or reprogramming of the tumor microenvironment.
“We anticipate that our discovery will guide forthcoming studies seeking to understand and unravel the cellular paradigms of pancreatic cancer,” Atfi said.