Heme Oxygenase -1 (HO-1) in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer‬‬

ALEJANDRA PAEZ,; CARLA PALLAVICINI,; SCHUSTER FEDERICO,; MARIA PIA VALACCO; JIMENA GIUDICE ; EMILIANO ORTIZ,; NICOLAS ANSELMINO; LABANCA ESTEFANIA; MARIA BINAGHI,; MARCELO SALIERNO; MARCELO MARTI; JAVIER COTIGNOLA; WOLOSZYNSKA-READ, ANNA; LUCIANA BRUNO,; VALERIA LEVI ; NORA NAVONE; ELBA VAZQUEZ.

Mar del Plata

Congreso; LXI Reunion Anual Sociedad Argentina de Investigación Clinica; 2016

Sociedad Argentina de Investigación Clinica

Prostate Cancer (PCa) cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity to resist chemotherapy and colonize distant organs. We have previously shown that heme-oxygenase 1 (HO-1) is implicated in cell morphology regulation in PCa. Here, through a multi ?omics? approach we define the HO-1 interactome in PCa, identifying HO-1 molecular 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 to normal prostate tissue. Under HO-1 induction, PCa cells present reduced frequency in migration events, trajectory and cell velocity and, a significant higher proportion of filopodia-like protrusions among neighboring cells. Moreover forced-expression of HO-1 was also capable 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 markers related to cell adhesion and cell-cell communication under HO-1 induction. The integration from our omics-based research provides a four molecular pathway foundation (ANXA2/HMGA1/POU3F1; NFRSF13/GSN; TMOD3/RAI14/VWF; PLAT/PLAU) behind HO-1 regulation of tumor cytoskeletal cell compartments. The complementary proteomics and transcriptomics approaches presented here promise to move us closer to unravel the molecular framework underpinning HO-1 involvement in the modulation of cytoskeleton pathways, pushing towards a less aggressive phenotype, showcasing its relevance as a key homeostatic factor against the aggressive disease.