IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
HO-1: The Mastermind Behind the Morphology and the Adhesive Behavior of Prostate Cancer Cells
Autor/es:
GERALDINE GUERON; JIMENA GIUDICE; VALACCO PIA; BELEN ELGUERO; PAEZ A; TOSACNI ANDRES MARTIN; JAWORSKI F; COLUCCIO LESKOW FEDERICO; COTIGNOLA J; MARTI M; BINAGHI M; NAVONE, N; ELBA VAZQUEZ
Lugar:
National Harbor
Reunión:
Congreso; 20TH ANNUAL PCF SCIENTIFIC RETREAT; 2013
Institución organizadora:
Prostate Cancer Foundation
Resumen:
Background: Prostate Cancer (PCa) is the second leading cause of cancer death in
American men. The loss of cell-cell adhesion is frequently associated with the
progression to a metastatic state. Although previous studies about cell adhesion in
PCa have focused on adherens junctions (AJs), key players in the integrity of the
epithelium, they have left the molecular mechanisms unexplored. Heme Oxygenase-
1 (HO-1) acts as a cellular rheostat counteracting oxidative and inflammatory
damage1. We previously showed that HO-1 over-expression impaired tumor growth
and angiogenesis in vivo2-3. Given that inflammation is critical for the development
and progression of PCa4, we assessed whether HO-1 could regulate the adhesive
properties and the morphology of PCa cells.
Methods: GeneMANIA5, DAVID6 and Metacore were used as bioinformatics tools.
Immunofluorescence analyses and quantitative microscopy were done as previously
described7. GST-pull-down assays were performed using lysates from PC3 cells
transfected with either GST-tagged HO-1 or the empty vector, and the isolated
proteins were subjected to MALDI-TOF/TOF analyses.
Results: Genes differentially regulated by HO-1 were enriched for cell motility and
adhesion biological processes. Induction of HO-1 increased cell adhesion and E-
cadherin/β-catenin levels, the main cell adhesion molecules at AJs8. Furthermore, a
striking remodeling of E-cadherin/β-catenin-based AJs was also observed, consistent
with a marked change in cell morphology. In an effort to understand the molecular
mechanisms underlying HO-1?s role in cell morphology regulation we used a
proteomics approach to identify HO-1 partners. Our results showed that HO-1
interacts with Muskelin9, which has been strongly implicated in cell morphology
regulation.
Conclusion: These results define a novel role for HO-1 in modulating the
architecture of cell-to-cell interactions, favoring a less aggressive phenotype and
further supporting its anti-tumoral function in PCa.