Oncotarget

Research Papers:

Heme-oxygenase-1 implications in cell morphology and the adhesive behavior of prostate cancer cells

Geraldine Gueron _, Jimena Giudice, Pia Valacco, Alejandra Paez, Belen Elguero, Martin Toscani, Felipe Jaworski, Federico Coluccio Leskow, Javier Cotignola, Marcelo Marti, Maria Binaghi, Nora Navone and Elba Vazquez

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Oncotarget. 2014; 5:4087-4102. https://doi.org/10.18632/oncotarget.1826

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Abstract

Geraldine Gueron1, Jimena Giudice2, Pia Valacco3,  Alejandra Paez1, Belen Elguero1, Martin Toscani1, Felipe Jaworski1, Federico Coluccio Leskow1, Javier Cotignola1, Marcelo Marti1, Maria Binaghi1, Nora Navone4, Elba Vazquez1

1 Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Intendente Guiraldes 2160, CABA

2 Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA

3 CEQUIBIEM-Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET

4 Department of Genitourinary Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA

Correspondence:

Geraldine Gueron, email:

Elba Vazquez, email:

Keywords: Prostate Cancer, Heme-oxygenase-1, Muskelin, E-cadherin, B-catenin, Adherens Junctions,

Received: January 24, 2014 Accepted: March 14, 2014 Published: March 16, 2014

Abstract

Prostate cancer (PCa) is the second leading cause of cancer death in men. Although previous studies in PCa have focused on cell adherens junctions (AJs), key players in metastasis, they have left the molecular mechanisms unexplored. Inflammation and the involvement of reactive oxygen species (ROS) are critical in the regulation of cell adhesion and the integrity of the epithelium. Heme oxygenase-1 (HO-1) counteracts oxidative and inflammatory damage. Here, we investigated whether HO-1 is implicated in the adhesive and morphological properties of tumor cells. Genes differentially regulated by HO-1 were enriched for cell motility and adhesion biological processes. HO-1 induction, increased E-cadherin and β-catenin levels. Immunofluorescence analyses showed a striking remodeling of E-cadherin/β-catenin based AJs under HO-1 modulation. Interestingly, the enhanced levels of E-cadherin and β-catenin coincided with a markedly change in cell morphology. To further our analysis we sought to identify HO-1 binding proteins that might participate in the regulation of cell morphology. A proteomics approach identified Muskelin, as a novel HO-1 partner, strongly implicated in cell morphology regulation. These results define a novel role for HO-1 in modulating the architecture of cell-cell interactions, favoring a less aggressive phenotype and further supporting its anti-tumoral function in PCa. 


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