Development of new anticancer therapeutic strategies based on proteomic analysis of signal transduction pathways relevant in cancer stem cells

Research project

Description

Tumors are characterized by alterations of the signal transduction pathways that regulate cell growth. In various tumors it has been described that such alterations affect cells with stem cell properties (cancer stem cells - CSC). The CSCs are reported as a reservoir of tumor cells, because of their ability to self-renew. Thus, they are able to maintain the tumor mass by producing differentiated lines of tumor cells. A better understanding of the pathways involved in self-renewal is therefore essential to clarify the functional behavior of these cells. In addition, the development and application of advanced proteomics techniques help to study on one hand the interconnections among different signal transduction pathways involved in self-renewal of cancer stem cells and, on the other hand, post-translational modifications of proteins involved in these pathways. This can significantly contribute to the identification of biomarkers critical for diagnosis, prognosis and therapy of brain a,nd colon tumors.
The main aim of this project is to develop an integrated molecular model useful to characterize the role of specific signal transduction pathways in regulating cancer stem cells survival and proliferation. The research includes isolation and characterization of CSC of cerebral cancers (glioblastoma and medulloblastoma) and colon carcinomas and the use of genomic techniques (new generation Deep-sequencing) and advanced proteomics in the purpose to identify mechanisms and molecoles involved in Hedgehog and Notch signal transduction, that regulate CSC self-renewal, and finally to individuate new specific therapeutic target, more effective because directed against a tumorigenic cell population.
Taking into account the key role played by Hh and Notch signaling pathways in regulating cell proliferation and differentiation, the final aim of the project is to analyze the molecular mechanims triggered and/or sustained by these pathways and involved in regulating the self-rene,wal and proliferation of cancer stem cells within the tumors.
StatusActive
Effective start/end date1/1/11 → …

Funding

  • MIUR - FIRB

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Neoplastic Stem Cells
Proteomics
Signal Transduction
Neoplasms
Colon
Cell Proliferation
High-Throughput Nucleotide Sequencing
Medulloblastoma
Molecular Models
Hedgehogs
Post Translational Protein Processing
Glioblastoma
Tumor Cell Line
Cell Differentiation
Cell Survival
Stem Cells
Biological Markers
Carcinoma
Brain