HITTING THE BRAKES ON THE MIGRATORY CAPACITY OF TUMORAL CELLS: TARGETING KEY REGULATORS OF ACTIN DYNAMICS IN PROSTATE CANCER.

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

Nueva Orleans

Congreso; American Association for Cancer Research (AACR) Annual Meeting; 2016

American Association for Cancer Research

Prostate Cancer (PCa) is the second leading cause of cancer in men. PCa cells display abnormal expression of cytoskeletal proteins resulting in an augmented capacity toresist chemotherapy and colonize other organs. We have previously shown that hemeoxygenase1 (HO1)has a strong antitumoraleffect in prostate cancer (PCa) andregulates the adhesive properties of PCa cells. Innovative highthroughputproteomic platforms are now identifying and quantifying new specific and sensitive biomarkers forPCa detection, stratification and treatment. Towards this end, we undertook an indepthmass spectrometrybasedproteomics study to build the Hemeoxygenase1 (HO1)interactome in PCa, in an effort to identify HO1molecular partners associated to the integrity of the cellular architecture and assess actin dynamics of PCa cells under HO1modulation.The proteomics analysis of HO1interacting proteins yielded several cytoskeletalassociatedproteins regulating actin filament dynamics, such as gelsolin, lasp1, SIPA1L1,testin, moesin, tropomodulin and vinculin. The bioinformatics screening across the Oncomine platform revealed that the RNA expression profiles of the cytoskeletal HO1interacting proteins, lie within the 10 percent of the most consistently lowexpressedgenes in prostate adenocarcinoma compared to normal tissue.Motility changes were assessed on fiberlike2D migration scenarios displaying a reduced frequency in migration events and in migration speed under hemin exposure, aspecific pharmacological inducer of HO1.A significant higher proportion of filopodialikeprotrusions among neighboring cells and cellular contacts were observed when HO1was induced; effects reversed under HO1silencing. Altogether, our experimental findings demonstrate that HO1modulation in PCa induces the remodeling of the actinfilament architecture at filopodia, alters the migratory patterns and cellular morphology, showcasing the relevance of the cytoskeletal proteins as potential therapeutic targetsagainst the aggressive and metastatic disease.