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01-06-2016 | Research Paper

Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells

Authors: Tonielli Cristina Sousa de Lacerda, Bruno Costa-Silva, Fernanda Salgueiredo Giudice, Marcos Vinicios Salles Dias, Gabriela Pintar de Oliveira, Bianca Luise Teixeira, Tiago Goss dos Santos, Vilma Regina Martins

Published in: Clinical & Experimental Metastasis | Issue 5/2016

Abstract

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. The generation of conventional treatments has improved, but approximately 50 % of patients with CRC who undergo potentially curative surgery ultimately relapse and die, usually as a consequence of metastatic disease. Our previous findings showed that engagement of the cellular prion protein (PrP^C) to its ligand HSP70/90 heat shock organizing protein (HOP) induces proliferation of glioblastomas. In addition, PrP^C has been described as an important modulator of colorectal tumor growth. Here, we investigated the biological relevance of the PrP^C-HOP interaction in CRC cells. We demonstrate that HOP induced the migration and invasion of CRC cell lines in a PrP^C-dependent manner and that phosphorylation of the ERK1/2 pathway is a downstream mediator of these effects. Additionally, we show that a HOP peptide with the ability to bind PrP^C and abolish the PrP^C-HOP interaction inhibited the migration and invasion of CRC cells. Together, these data indicate that the disruption of the PrP^C-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic CRC.

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Title: Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells
Authors: Tonielli Cristina Sousa de Lacerda
Bruno Costa-Silva
Fernanda Salgueiredo Giudice
Marcos Vinicios Salles Dias
Gabriela Pintar de Oliveira
Bianca Luise Teixeira
Tiago Goss dos Santos
Vilma Regina Martins
Publication date: 01-06-2016
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 5/2016
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-016-9788-8

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