Integrated interactome, proteomic and functional analyses reveal molecular pathways driving L1TD1-induced aggressiveness in CNS embryonal tumor cells

Author(s)

Mitsugi, Thiago Giove ; Sherwood, Matt ; Jandrey, Elisa Helena Farias ; Assoni, Amanda Faria ; Bell, Joseph ; Coke, Brandon ; Skipp, Paul ; Ewing, Rob ; Okamoto, Oswaldo Keith

• Document type: Journal article
• Source: FEBS Letters; v. N/A, p. 17-pg., 2025-02-06.

Abstract

L1TD1 is a pluripotency factor required for embryonic stem cell self-renewal; its expression has also been detected in solid tumors, including embryonal tumors of the central nervous system (CNS). Previously, we showed that L1TD1 expression correlates with metastasis formation and shorter overall survival of medulloblastoma patients. Here, we used affinity purification coupled to mass spectrometry to map the L1TD1 interactome, and global proteomics to assess proteins differentially regulated by L1TD1 expression in patient-derived embryonal CNS tumor cell lines. We identified novel L1TD1 interactors and differentially expressed proteins related to cell proliferation, death and motility. Finally, we demonstrated that L1TD1-overexpressing tumor cells have distinct cell morphology with enhanced filopodial formation, higher cell motility, greater proliferation capability, and reduced sensitivity to cisplatin treatment. (AU)

• FAPESP's process: 21/00689-5 - Development of a chimeric antigen receptor for application on glioblastoma treatment
• Grantee: Thiago Giove Mitsugi
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/50021-2 - Cancer stem cell interactome mapping
• Grantee: Oswaldo Keith Okamoto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/20373-0 - Characterization of the proteic interactoma of the pluripotency factor L1TD1 in central nervous system tumour stem cells and neural stem cells
• Grantee: Thiago Giove Mitsugi
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC