Characterization of the proteic interactoma of the pluripotency factor L1TD1 in central nervous system tumour stem cells and neural stem cells

• Grant number: 18/20373-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2018
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Thiago Giove Mitsugi
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID

Abstract

Medulloblastoma is the most common type of malignant Central Nervous System (CNS) embryonal cancer in children up to 4 years of age and is one of the leading causes of childhood morbidity and mortality. Stem cells and tumor cells have been shown to have some common pluripotency properties that have been associated with tumorigenicity in several types of solid cancers. In medulloblastoma the expression of pluripotency factors such as OCT4 and Lin28 are correlated with worse clinical prognosis and formation of metastasis. Several factors linked to the maintenance of the pluripotent state in human cells have been studied, but most of these factors remain poorly characterized, such as the L1TD1 RNA binding protein. L1TD1 is a protein present in normal stem cells but without detectable expression in adult somatic tissues, and its expression is suppressed in the early stages of cell differentiation. However, in some types of tumors the expression of L1TD1 is observed to be strongly regulated by the expression of pluripotency maintenance factors and other neural stem-cell markers such as CD133. In the present study we propose to investigate the protein interatome of tumor stem cell lines, focusing on the interaction of L1TD1 protein. To do this we will overexpress GFP-fused L1TD1 protein to co-immunoprecipitate the protein and its protein binders, which will be analyzed by mass spectrometry in collaboration with the Laboratory of Prof. Dr. Rob Ewing from Southampton University (UK).