Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell?cell contacts and filopodia-induced zippering in prostate cancer

PAEZ, ALEJANDRA VERÓNICA; PALLAVICINI, CARLA; SCHUSTER, FEDERICO; VALACCO, PIA; ORTIZ EMILIANO GERMAN; VAZQUEZ, ELBA SUSANA; GUERON, G; LEVI, VALERIA; NAVONE, NORA; WOLOSZYNSKA-READ, ANNA; COTIGNOLA, JAVIER; MARTI MARCELO; ANSELMINO, NICOLÁS; LABANCA, ESTEFANIA; BRUNO, LUCIANA; BINAGHI, MARIA; SALIERNO MARCELO

Cell Death Disease

Dept Experimental Medicine, Sala D26

Lugar: Roma ; Año: 2016 vol. 7

Prostate Cancer (PCa) cells display abnormal expression of cytoskeletalproteins resulting in an augmented capacity to resist chemotherapy andcolonize distant organs. We have previously shown that heme-oxygenase 1(HO-1) is implicated in cell morphology regulation in PCa. Here, through amulti ?omics? approach we define the HO-1 interactome in PCa, identifyingHO-1 molecular partners associated with the integrity of the cellularcytoskeleton. The bioinformatics screening for these cytoskeletal-relatedpartners reveal that they are highly misregulated in prostateadenocarcinoma compared to normal prostate tissue. Under HO-1 induction, PCacells present reduced frequency in migration events, trajectory and cellvelocity and, a significant higher proportion of filopodia-like protrusionsfavoring zippering among neighboring cells. Moreover forced-expression ofHO-1 was also capable of altering cell protrusions in transwell co-culturesystems of PCa cells with MC3T3 cells (pre-osteoblastic cell line).Accordingly, these effects were reversed under siHO. Transcriptomicsprofiling evidenced significant modulation of key markers related to celladhesion and cell-cell communication under HO-1 induction. The integrationfrom our omics-based research provides a four molecular pathway foundation(ANXA2/HMGA1/POU3F1; NFRSF13/GSN; TMOD3/RAI14/VWF; PLAT/PLAU) behindHO-1 regulationof tumor cytoskeletal cell compartments. The complementary proteomics andtranscriptomics approaches presented here promise to move us closer tounravel the molecular framework underpinning HO-1 involvement in themodulation of cytoskeleton pathways, pushing towards a less aggressivephenotype in PCa.