A research team from the University of Texas Health Science Center at Houston (UTHealth) and Baylor College of Medicine say they have identified a novel molecular mechanism that contributes to the spread of malignant tumors in the pancreas. Now a major goal is to develop therapies to block this pathway.
The study, published in EMBO Molecular Medicine, focused on the previously established link between zinc and pancreatic cancer and sought to identify a molecular mechanism responsible for the elevated levels found in human and animal cells.
“We were the first to show that zinc transporter ZIP4 was a marker for pancreatic cancer,” said Min Li, Ph.D., the study’s senior author and associate professor and director of the cancer research program in the Vivian L. Smith Department of Neurosurgery at the UTHealth Medical School. “We knew there was a link but we didn’t know what it was.”
Zinc levels are regulated by ZIP4, which acts as a master switch, and the researchers designed experiments to determine what happens when the switch is flipped on, noted Dr. Li.
In a xenograft mouse model of pancreatic cancer, the scientists observed how the initiation of ZIP4 triggered the activation of two downstream genes, which in turn accounts for the increased tumor growth. Scientists describe this as a signaling cascade.
“Pancreatic cancer is among the worst of all cancers. It is imperative to define the mechanism of this deadly disease. We have recently demonstrated a novel biological role for the zinc transporter ZIP4 in pancreatic cancer,” explained Yuqing Zhang, Ph.D., co-first author of the study. “However, the molecular pathway controlling this phenomenon remains elusive. This study provides a comprehensive mechanism for ZIP4-mediated pancreatic cancer growth involving the activation of a transcription factor CREB and an oncogenic miR-373, and reduction in key tumor suppressor genes.”
“The results we reported in this study may help the design of future therapeutic strategies targeting the zinc transporter and microRNA pathways to treat pancreatic cancer,” added said Xiaobo Cui, M.D., Ph.D., study co-first author and postdoctoral research fellow at the UTHealth Medical School.