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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Prostate Cancer | Primary research

SFRP1 increases TMPRSS2-ERG expression promoting neoplastic features in prostate cancer in vitro and in vivo

Authors: Carlos D. Cruz-Hernández, Marian Cruz-Burgos, Sergio A. Cortés-Ramírez, Alberto Losada-García, Ignacio Camacho-Arroyo, Patricia García-López, Elizabeth Langley, Vanessa González-Covarrubias, Monserrat Llaguno-Munive, Martha E. Albino-Sánchez, José L. Cruz-Colín, Carlos Pérez-Plasencia, Fredy O. Beltrán-Anaya, Mauricio Rodríguez-Dorantes

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Prostate cancer (PCa) is the second cause of cancer related death in North American men. Androgens play an important role in its progression by regulating the expression of several genes including fusion ones that results from structural chromosome rearrangements. TMPRSS2-ERG is a fusion gene commonly observed in over 50% of PCa tumors, and its expression can be transcriptionally regulated by the androgen receptor (AR) given its androgen responsive elements. TMPRSS2-ERG could be involved in epithelial–mesenchymal transition (EMT) during tumor development. ERG has been reported as a key transcriptional factor in the AR-ERG-WNT network where five SFRP proteins, structurally similar to WNT ligands and considered to be WNT pathway antagonists, can regulate signaling in the extracellular space  by binding to WNT proteins or Frizzled receptors. It has been shown that over-expression of SFRP1 protein can regulate the transcriptional activity of AR and inhibits the formation of colonies in LNCaP cells. However, the effect of SFRP1 has been controversial since differential effects have been observed depending on its concentration and tissue location. In this study, we explored the role of exogenous SFRP1 protein in cells expressing the TMPRSS2-ERG fusion.

Methods

To evaluate the effect of exogenous SFRP1 protein on PCa cells expressing TMPRSS2-ERG, we performed in silico analysis from TCGA cohort, expression assays by RT-qPCR and Western blot, cell viability and cell cycle measurements by cytometry, migration and invasion assays by xCELLigance system and murine xenografts.

Results

We demonstrated that SFRP1 protein increased ERG expression by promoting cellular migration in vitro and increasing tumor growth in vivo in PCa cells with the TMPRSS2-ERG fusion.

Conclusions

These results suggest the possible role of exogenous SFRP1 protein as a modulator of AR-ERG-WNT signaling network in cells positive to TMPRSS2-ERG. Further, investigation is needed to determine if SFRP1 protein could be a target in against this type of PCa.
Appendix
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Metadata
Title
SFRP1 increases TMPRSS2-ERG expression promoting neoplastic features in prostate cancer in vitro and in vivo
Authors
Carlos D. Cruz-Hernández
Marian Cruz-Burgos
Sergio A. Cortés-Ramírez
Alberto Losada-García
Ignacio Camacho-Arroyo
Patricia García-López
Elizabeth Langley
Vanessa González-Covarrubias
Monserrat Llaguno-Munive
Martha E. Albino-Sánchez
José L. Cruz-Colín
Carlos Pérez-Plasencia
Fredy O. Beltrán-Anaya
Mauricio Rodríguez-Dorantes
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01333-5

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