Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells
Clinical & experimental metastasis(2016)
摘要
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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关键词
Prion protein,HOP protein,Colorectal cancer,Invasion,Migration
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