Melanoma migration is promoted by prion protein via Akt-hsp27 signaling axis.

Abstract

Patients with metastatic melanoma have a poorer prognosis. Prion protein (PrP) in melanoma is known to play an important role in cancer cell migration and invasion by interacting with filamin A (FLNa), a cytolinker protein. To investigate if PrP may contribute to cancer cell mobility independent of its binding to FLNa, we knocked out PRNP in M2 melanoma cell, which lacked FLNa expression. We found that deletion of PRNP in M2 significantly reduced its motility. When PRNP was deleted, the level of Akt was decreased. As a consequence, phosphorylation of small heat shock protein (hsp27) was also reduced, which resulted in polymerization of F-actin rendering the cells less migratory. Accordingly, when PrP was re-expressed in PRNP null M2 cells, the mobility of the recurred cells was rescued, so were the expression levels of Akt and phosphorylated hsp27, resulting in a decrease in the polymerization of F-actin. These results revealed that PrP can play a FLNa independent role in cytoskeletal organization and tumor cell migration by modulating Akt-hsp27-F-actin axis.

• Authors: Jingru Ke, Guiru Wu, Jie Zhang, Huan Li, Shanshan Gao, Ming Shao, Zhenxing Gao, Man-Sun Sy, Yuchun Cao, Xiaowen Yang, Jiang Xu, Chaoyang Li
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 523 Issue 2 Pg. 375-381 (03 05 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 31870551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Actins
• FLNA protein, human
• Filamins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Prion Proteins
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases

Topics

• Actins (metabolism)
• Cell Line, Tumor
• Cell Movement (physiology)
• Filamins (deficiency, genetics, metabolism)
• Gene Knockout Techniques
• Gene Silencing
• Heat-Shock Proteins (metabolism)
• Humans
• Melanoma (genetics, metabolism, pathology)
• Molecular Chaperones (metabolism)
• Neoplasm Invasiveness (pathology, physiopathology)
• Prion Proteins (deficiency, genetics, metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (metabolism)