title: Heme-oxygenase-1 implications in cell morphology and the  adhesive behavior of prostate cancer cells.
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.
authors: Geraldine
authors: G
authors: Gueron
authors: Jimena
authors: J
authors: Giudice
authors: Pia
authors: P
authors: Valacco
authors: Alejandra
authors: A
authors: Paez
authors: Belen
authors: B
authors: Elguero
authors: Martin
authors: M
authors: Toscani
authors: Felipe
authors: F
authors: Jaworski
authors: Federico Coluccio
authors: FC
authors: Leskow
authors: Javier
authors: J
authors: Cotignola
authors: Marcelo
authors: M
authors: Marti
authors: Maria
authors: M
authors: Binaghi
authors: Nora
authors: N
authors: Navone
authors: Elba
authors: E
authors: Vazquez
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D015536:Down-Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D017382:Reactive Oxygen Species; D051176:beta Catenin; D051547:Heme Oxygenase-1