IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
artículos
Título:
Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell–cell contacts and filopodia-induced zippering in prostate cancer
Autor/es:
CARLA PALLAVICINI; JIMENA GIUDICE; ESTEFANÍA LABANCA; CARLA PALLAVICINI, VALERIA LEVI, LUCIANA BRUNO, MARCELO A. DESPÓSITO.; LUCIANA BRUNO; ELBA S VAZQUEZ; ALEJANDRA PAEZ; MARIA PIA VALACCO; NICOLÁS ANSELMINO; MARCELO SALIERNO; ANA WOLOSZYNSKA-READ; NORA NAVONE; FEDERICO SCHUSTER ; EMILIANO G. ORTIZ; MARIA BINAGHI; JAVIER H COTIGNOLA; VALERIA LEVI; GERALDINE GUERON
Revista:
Cell death and disease
Editorial:
London : Nature Pub. Group
Referencias:
Año: 2016 vol. 7
Resumen:
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 with 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 favoring zippering 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; and 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 toward a less aggressive phenotype in PCa.