Understanding the dual role of WIP as oncogene and tumor suppressor
Ponente: Inés Antón
Centro Nacional de Biotecnología (UAM/CSIC) [Madrid]
Host: Miguel Vicente Manzanares
Salón de Actos del Centro de Investigación del Cáncer
(WASP Interacting Protein) is part of a regulatory complex for actin polymerization, an essential process for cell migration and tumor invasion, and is expressed differentially in cancer stem cells (CSC). The most recent tumor therapies are directed towards the elimination of these cells as they are the most resistant to chemotherapy. Our results indicate that WIP exhibits opposite dual activity in its contribution to oncogenic development, acting as tumor suppressor in large cell anaplastic lymphomas (ALCL) and as an oncogene in TICs of solid tumors, both in breast cancer and in glioblastomas. More especifically, our research interest focuses on the role of actin-binding elements in the regulation of Akt-mediated signalling routes controlling invasiveness, survival and tumorigenesis. Our work showed that WIP is preferentially expressed in invasive tumor samples (glioblastoma and breast cancer) and affect tumor phenotype at two levels: 1) initiation, as it participates in the establishment and maintenance of CSC preventing their apoptotic caspase-dependent cell death; 2) progression, as it promotes CSC capacity to degrade the extracellular matrix contributing to invasiveness and metastasis. WIP expression leads to the sequestration of the destruction complex in multivesicular bodies and thus promotes the stability of the transcriptional co-activators YAP/TAZ. WIP is also an essential part of a p53-mediated oncogenic cascade that maintain tumour growth capacity and the stem phenotype. Our findings demonstrate an oncogenic role for WIP in solid tumors through an Akt-related developmental/oncogenic axis and hopefully they will contribute to find new biomarkers and therapeutic targets to fight metastases. Using qualitative and quantitative proteomics approaches, we work to identify how the WIP interactome changes between tumors of hematopoietic and non-hematopoietic origin to identify potential therapeutic targets that facilitate the search of specific tumor therapies in each system. We are confident that the results derived from our work will contribute to identify compounds and/or genetic tools to reach the challenge of improving the quality of life of cancer patients and reducing tumor-associated deaths.