An integrated proteomic portrait of prostate cancer progression
Institute of Oncology Research
The Functional Cancer Genomics research group, led by Prof. Jean-Philippe Theurillat at the Institute of Oncology Research (IOR, affiliated to USI and member of Bios+), has recently published a paper describing proteomic changes along prostate cancer progression. The study, conducted in close collaboration with the Broad Institute of MIT & Harvard revealed the involvement of thus far underappreciated molecular mechanisms related to disease aggressiveness. A web-based resource enables the research community to interrogate the complex data set (www.prostatecancerprogression.org). The study is published in Cell Reports.
Background
Prostate cancer emerges from the malignant transformation of the prostate epithelium. Upon tumor formation in the prostate, tumor cells can spread to distant organs, such as the bone. At this stage, the disease is typically treated with by drugs that suppress the androgen receptor, the key oncogene. Nevertheless, in some instances, tumor cells can develop resistance to the treatment, which is associated with fatal outcomes in most cases.
While this roadmap of prostate cancer progression has been extensively studied at the genome level, associated changes of proteins or their post-translational modification remain largely uncharacterized in this regard.
The discovery
Prof. Theurillat and colleagues conducted a larger-scale study to decipher protein expression changes and changes in the abundance of post-translational modifications which may in turn modify protein activity during prostate cancer progression. The group identified thus far unrecognized pathways and protein modifications associated with disease. Among these, frequent inactivation of the neurofibromatosis 1 (NF1) tumor suppressor through protein downregulation, activation of the oncogene NRAS through protein de-ubiquitylation, or inactivation of the tumor suppressor ERF through increased phosphorylation. The insights may open new perspectives for drug development efforts aimed at preventing prostate cancer progression with current therapies
Outlook
The findings of this study revealed may new potential drug targets which will need to be explored in the future.
The study: An integrated proteomic portrait of prostate cancer progression
