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

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

  • Am J Pathol. 2020 Sep;190(9):1931-1942. doi: 10.1016/j.ajpath.2020.05.018.
Fangfang Gao 1,  Nathan Griffin 1,  Sam Faulkner 1,  Xiang Li 1,  Simon J King 2,  Phillip Jobling 1,  Jim W Denham 2,  Chen Chen Jiang 3,  Hubert Hondermarck 4
Affiliations

Affiliations

  • 1 School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, New South Wales, Australia.
  • 2 Hunter Medical Research Institute, University of Newcastle, New Lambton, New South Wales, Australia.
  • 3 School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, New South Wales, Australia.
  • 4 School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, Australia; Hunter Medical Research Institute, University of Newcastle, New Lambton, New South Wales, Australia. Electronic address: hubert.hondermarck@newcastle.edu.au.
PMID: 32526166 DOI: 10.1016/j.ajpath.2020.05.018
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.

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