Research Sheds New Light on Pancreatic Cancer Metastasis; Zinc Transporter ZIP4 Plays Key Role in Transition of Pancreatic Tumor Cells from Epithelial to Mesenchymal Phenotype, Enhancing Metastasis

With an overall survival rate of just 9% for those diagnosed, pancreatic cancer remains exceedingly difficult to treat. However, the patient's primary tumor typically isn't what leads to death--it is the cancer's ability to evade detection and metastasize to other organs. A team of researchers at the Oklahoma University (OU) College of Medicine has published a new study in the April 1, 2021 issue of Gastroenterology, the world's leading publication on GI tract disease, that sheds new light on the ability of pancreatic cancer cells to spread throughout the body. The article is titled “Zinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer” ( Understanding why metastasis occurs is crucial for developing a therapeutic strategy to stop the spread. The study, led by scientist Min Li, PhD, and physician-scientist Courtney Houchen (photo), MD, centers around ZIP4, a protein that transports zinc throughout the body. While zinc is important for good health, too much of the heavy metal causes problems. In the new study, researchers found that when ZIP4 is overexpressed in patients with pancreatic cancer, it essentially prompts the tumor cells to transform themselves in a manner that allows them to stealthily travel to the body's other organs. In scientific terms, the tumor cells transition from an epithelial to a mesenchymal phenotype. "That transition means the tumor cells are doing everything they can to avoid the surveillance of the body's immune system, as well as chemotherapy and other therapies," Dr. Li said. "They become more evasive and are able to penetrate the blood vessels, which permits them to go anywhere in the body."
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