AIRC-MFAG-18535 (DSB.AD006.186)
Thematic area
Project area
Biologia Molecolare/Cellulare (DSB.AD006)Structure responsible for the research project
Institute of biomedical technologies (ITB)
Other structures collaborating in the research project
Project manager
FABIO MAMMANO
Phone number: 0690091307
Email: fabio.mammano@cnr.it
Abstract
Pathologists often define irregularity in the nuclear morphology coupled with alterations in heterochromatin higher order structures as a hallmark of cancer aggressiveness. Although emerging evidence indicate that perturbation of nuclear parameters, such as high order chromatin structures and nuclear architecture, represent early steps preceding tumour transformation toward
aggressive forms, the molecular mechanisms and the pathways involved in this aberrant cascade of events are not described. We believe that the Polycomb group of proteins (PcG), epigenetic regulators of heterochromatin, assume a position in the nucleus that is highly controlled and required for their functions. In pathological cancer conditions, repositioning of PcG proteins and/or specific genomic regions, assisted by nuclear structures, such as Lamin A/C, can determine heterochromatin reshaping. This could facilitate transition between epigenetic states, leading to an aberrant chromatin usage and to an uncontrolled exposure of specific genomic regions to mutagenesis, finally determining a survival advantage for cancer cells.
Goals
The general strategy of our project aims at uncovering the role of nuclear architecture in Prostate Cancer (PCa), from two different points of view, genome and protein architectures, with the final goal of enlightening about the underlying mechanisms of PCa progression.Using computational analysis of prostatic tissue images we will produce integrative maps of PcG foci positioning predictive of the PCa state. The formal demonstration that PcG proteins occupy predetermined position in the nucleus and that this localization influences their activity in cancer progression will corroborate findings showing that specific nuclear microenvironment are permissive for specific biological functions, further suggesting that precise positioning can influence
genome activity. Further identification of tumour subclones showing specific PcG "texture" could improve stratification of the cancer population, potentially leading to an identification of nuclei subsets responsible of cancer progression and/or that over time are informative of the subsequent phases of a PCa pathological process.
Start date of activity
31/07/2017
Keywords
polycomb, prostate cancer, nuclear architecture
Last update: 19/04/2024