[PDLIM2 and Its Role in Oncogenesis--Tumor Suppressor or Oncoprote?]. / PDLIM2 a jeho role v onkogenezi--tumor supresor nebo onkoprotein?

PDZ and LIM domain containing protein 2 (PDLIM2), also known as Mystique or SLIM, is a member of the actinin-associated LIM family of proteins that play essential roles in cytoskeletone organization, cell differentiation and have been associated with oncogenesis. PDLIM2 is cytoskeletal and nuclear protein encoded by the Mystique gene localized on chromosome 8p21. PDLIM2 regulates stability and activity of several transcription factors, e. g. NF  κB or STAT, and its deregulation is associated with several malignancies. PDLIM2 expression has been connected with both tumor suppression and tumorigenesis. PDLIM2 levels are epigenetically suppressed in different cancers due to Mystique promoter hypermetylation that blocks its transcription. PDLIM2 re expression is able to inhibit tumorigenicity and induces tumor cell death both in vitro and in vivo, which suggest potential tumor suppressor role of PDLIM2. On the other hand, PDLIM2 is highly expressed in cancer cell lines derived from metastatic cancer and its expression is associated with tumor progression and metastasis formation, indicating pro oncogenic role of PDLIM2. The aim of this review is to summarize current knowledge on the role of PDLIM2 in tumor formation and development, focusing on its prospective role as therapeutic target and offering potential explanations of its different functions in oncogenesis that were identified so far.

Identification and characterisation of pro-metastatic targets, pathways and molecular complexes using a toolbox of proteomic technologies.

BACKGROUND: Cancer metastasis involves changes in signalling pathways, cell adhesion, migration and invasiveness. Modern proteomic, mass spectrometry based techniques enable discovery of new pro-metastatic proteins and their functional partners. Also, they might be involved in their functional characterisation and validation towards development of new diagnostic and therapeutic approaches. AIM: The aim of this communication is to describe current possibilities for proteomic techniques in the discovery and characterization of pro-metastatic targets. The NF-kappaB pathway is one of the players responsible for a number of pro-metastatic processes. The related proteins can be discovered using untargeted proteomic approaches by comparing proteomes with different metastatic potential. Stable isotope labelling based methods enable a parallel analysis of more tumour samples. The identified pro-metastatic proteins can be characterised in relationship to cell migration, invasiveness and proliferation and in terms of their involvement in molecular complexes via protein-protein interactions. Advantages of the metabolic labelling based methods can be taken in these studies, the same applies for characterisation of related surface proteins involved in cell adhesion, invasiveness and cell-to-cell communication. For clinical validation of pro-metastatic proteins in large sample cohorts, approaches of targeted proteomics based on selected reaction monitoring are becoming methods of choice. CONCLUSION: Current proteomics methods play an important role in the identification of novel pro-metastatic proteins, pathways and molecular complexes, in their functional characterisation and validation towards diagnostic and therapeutic application.