Research projects

Recent discoveries highlight the ability of actin-related elements to control tumorigenesis and cell invasiveness through the regulation of signaling routes and transcription. Using WIP (Wiskott-Aldrich Syndrome Protein Interacting Protein) as model actin-binding protein, we demonstrated that WIP is expressed at high level in invasive/transformed cells from glioblastoma and breast cancer. Conversely, the reduction of WIP levels decreases significantly the proportion of cancer stem cells (CSC), the formation of invasive structures and the anchorage-independent growth, indicating that WIP acts as promoter of solid tumors. In collaboration with Harvard University researchers, we have described that, in contrast, WIP acts as a tumor suppressor in Anaplastic Large Cell Lymphoma (ALCL) since its absence favors the development of murine and human ALK+ (Anaplastic lymphoma kinase)-ALCL. 

The main goal of this project was to define the differential WIP interactome in each tumor type in order to identify the set of proteins and the molecular mechanisms that provides WIP with opposite functions. By using LC-MS/MS (Liquid-chromatography-mass spectrometry) and comparative bioinformatic analysis we have identified WIP-associated protein complexes specifically present in invasive glioblastoma cells (U87-MG grown as adherent cells or as CSC; 6 proteins) or in ALK+ lymphomas (JB6; 10 proteins). These results reveal a broad representation of components of metabolism, processes of synthesis of nitrogenous bases, pathways of protein degradation and intracellular transport. Based on these data, we have selected two proteins expressed in glioblastoma to confirm by functional biochemical and cellular tests their pro-oncogenic role: one related with protein degradation systems and another with intracellular signaling. We hope that the identification of these differential protein targets will contribute to future development of novel discriminating tumor biomarkers and effective oncological therapies directed to ALK+ lymphomas and specific CSC involved in solid tumor metastases, which are frequently resistant to treatments and accountable for tumor recurrence.