Impacto de la hemo oxygenasa 1 en la arquitectura celular: hacia un fenotipo menos agresivo en cáncer de próstata.

CARLA PALLAVICINI; EMILIANO G. ORTIZ; VALERIA LEVI; ALEJANDRA PAEZ; JIMENA GIUDICE; LUCIANA BRUNO; GERALDINE GUERON; FEDERICO SCHUSTER; NICOLÁS ANSELMINO; ELBA S VAZQUEZ

Buenos Aires

Simposio; Simposio Internacional Programa RAICES, Red de Científicos Argentinos en el Noreste de EE.UU. ?Ganando la guerra contra el cáncer?.; 2016

Prostate cancer (PCa) cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity to resistchemotherapy and colonize distant organs. We have previously shown that heme oxygenase 1 (HO-1) is implicated in cellmorphology regulation in PCa. Here, through a multi 'omics' approach we define the HO-1 interactome in PCa, identifying HO-1molecular partners associated with the integrity of the cellular cytoskeleton. The bioinformatics screening for these cytoskeletal-related partners reveal that they are highly misregulated in prostate adenocarcinoma compared with normal prostate tissue. UnderHO-1 induction, PCa cells present reduced frequency in migration events, trajectory and cell velocity and, a significant higherproportion of filopodia-like protrusions favoring zippering among neighboring cells. Moreover forced expression of HO-1 was alsocapable of altering cell protrusions in transwell co-culture systems of PCa cells with MC3T3 cells (pre-osteoblastic cell line).Accordingly, these effects were reversed under siHO. Transcriptomics profiling evidenced significant modulation of key markersrelated to cell adhesion and cell?cell communication under HO-1 induction. The integration from our omics-based researchprovides a four molecular pathway foundation (ANXA2/HMGA1/POU3F1; NFRSF13/GSN; TMOD3/RAI14/VWF; and PLAT/PLAU)behind HO-1 regulation of tumor cytoskeletal cell compartments. The complementary proteomics and transcriptomics approachespresented here promise to move us closer to unravel the molecular framework underpinning HO-1 involvement in the modulationof cytoskeleton pathways, pushing toward a less aggressive phenotype in PCa.