The Membrane Protein Sortilin Can Be Targeted to Inhibit Pancreatic Cancer Cell Invasion.

Abstract

Pancreatic cancer has a dismal prognosis, and there is no targeted therapy against this malignancy. The neuronal membrane protein sortilin is emerging as a regulator of cancer cell development, but its expression and impact in pancreatic cancer are unknown. This study found that sortilin expression was higher in pancreatic cell lines versus normal pancreatic ductal epithelial cells, as shown by Western blot analysis and mass spectrometry. The increased sortilin level in pancreatic cancer cells was confirmed by immunohistochemistry in a series of 99 human pancreatic adenocarcinomas versus 48 normal pancreatic tissues (P = 0.0014). Sortilin inhibition by siRNA and the pharmacologic inhibitor AF38469 strongly reduced the adhesion and invasion of pancreatic cancer cells without affecting cell survival and viability. Sortilin inhibition also decreased the phosphorylation of the focal adhesion kinase in Tyr925. Together, these data show that sortilin contributes to pancreatic cancer invasion and could eventually be targeted in therapy.

• Authors: Fangfang Gao, Nathan Griffin, Sam Faulkner, Xiang Li, Simon J King, Phillip Jobling, Jim W Denham, Chen Chen Jiang, Hubert Hondermarck
• Journal: The American journal of pathology (Am J Pathol) Vol. 190 Issue 9 Pg. 1931-1942 (09 2020) ISSN: 1525-2191 [Electronic] United States
• PMID: 32526166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Vesicular Transport
• sortilin

Topics

• Adaptor Proteins, Vesicular Transport (metabolism)
• Carcinoma, Pancreatic Ductal (metabolism, pathology)
• Cell Adhesion (physiology)
• Cell Movement (physiology)
• Humans
• Neoplasm Invasiveness (pathology)
• Pancreatic Neoplasms (metabolism, pathology)