Prion protein binding to HOP modulates the migration and invasion of colorectal cancer cells.
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.
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.|Department of Biochemistry, Institute of Chemistry, University of São Paulo (USP), Av. Prof. Lineu Prestes, 748 - Cidade Universitária, São Paulo, SP, 05508-000, Brazil.
Tonielli Cristina Sousa
TC
de Lacerda
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.|Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children's Health, Meyer Cancer Center, Weill Cornell Medical College, New York, NY, 10021, USA.|Champalimaud Research, Champalimaud Centre for the Unknown, Av. Brasilia, Doca de Pedrouços, 1400-038, Lisbon, Portugal.
Bruno
B
Costa-Silva
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.
Fernanda Salgueiredo
FS
Giudice
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.
Marcos Vinicios Salles
MV
Dias
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.
Gabriela Pintar
GP
de Oliveira
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.
Bianca Luise
BL
Teixeira
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil.
Tiago Goss
TG
Dos Santos
International Research Center, A.C.Camargo Cancer Center, Rua Taguá, 440 - Liberdade, São Paulo, SP, 01508-010, Brazil. vmartins@cipe.accamargo.org.br.
Vilma Regina
VR
Martins
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D000072002:Prion Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D060066:Protein Interaction Maps / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C476884:HOPX protein, human; D018398:Homeodomain Proteins; D000072002:Prion Proteins; D025521:Tumor Suppressor Proteins
Colorectal cancer; HOP protein; Invasion; Migration; Prion protein