Clinical & Experimental Metastasis

, Volume 33, Issue 5, pp 441–451 | Cite as

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

  • 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
Research Paper

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 (PrPC) to its ligand HSP70/90 heat shock organizing protein (HOP) induces proliferation of glioblastomas. In addition, PrPC has been described as an important modulator of colorectal tumor growth. Here, we investigated the biological relevance of the PrPC-HOP interaction in CRC cells. We demonstrate that HOP induced the migration and invasion of CRC cell lines in a PrPC-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 PrPC and abolish the PrPC-HOP interaction inhibited the migration and invasion of CRC cells. Together, these data indicate that the disruption of the PrPC-HOP complex could be a potential therapeutic target for modulating the migratory and invasive cellular properties that lead to metastatic CRC.

Keywords

Prion protein HOP protein Colorectal cancer Invasion Migration 

Notes

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2009/14027‐2) and National Institute for Science and Technology in Oncogenomics (INCITO). TCSL (11/18718-0), FSG (12/23285-8), MVSD (10/19200-1), GPO (13/26097-0) and BLT (11/20853-2) received fellowships from FAPESP.

Compliance with ethical standards

Conflict of Interest

The authors declare no conflict of interest.

Supplementary material

10585_2016_9788_MOESM1_ESM.tif (664 kb)
Supplementary material 1 (TIFF 664 kb). (A) Migration and (B) Invasion assays in WiDr and HCT8 cell lines. Cells were incubated on the top of boyden chambers coated with matrigel®; Serum-free DMEM or DMEM + 10 % FBS were used as chemoattractants. Data represent the average of at least four independent experiments ± standard error. [*p < 0.05 by Student’s t test]. (C) BrdU proliferation assay performed in WiDr CRC cells in conditions that mimicked the migration/invasion experiments. Cells were plated in 96 well plates and treated with recombinant HOP (5 µM) or 10 % FBS, a condition treated with 10 % FBS for 48 h was also included as positive control. Graph shows the levels of BrdUincorporation in relation to control, non-treated with HOP or FBS, and represents the average of at least four independent experiments ± standard error.

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Tonielli Cristina Sousa de Lacerda
    • 1
    • 2
  • Bruno Costa-Silva
    • 1
    • 3
    • 4
  • Fernanda Salgueiredo Giudice
    • 1
  • Marcos Vinicios Salles Dias
    • 1
  • Gabriela Pintar de Oliveira
    • 1
  • Bianca Luise Teixeira
    • 1
  • Tiago Goss dos Santos
    • 1
  • Vilma Regina Martins
    • 1
  1. 1.International Research CenterA.C.Camargo Cancer CenterSão PauloBrazil
  2. 2.Department of Biochemistry, Institute of ChemistryUniversity of São Paulo (USP)São PauloBrazil
  3. 3.Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer CenterWeill Cornell Medical CollegeNew YorkUSA
  4. 4.Champalimaud ResearchChampalimaud Centre for the UnknownLisbonPortugal

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