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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: FEBS Letters; v. N/A, p. 17-pg., 2025-02-06.

Resumo

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)

• Processo FAPESP: 21/00689-5 - Desenvolvimento de receptor quimérico de antígeno tumoral com aplicação no tratamento de glioblastoma
• Beneficiário: Thiago Giove Mitsugi
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 16/50021-2 - Cancer stem cell interactome mapping
• Beneficiário: Oswaldo Keith Okamoto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/20373-0 - Caracterização do interatoma proteico do fator de pluripotência L1TD1 em células-tronco tumorais e normais do sistema nervoso central
• Beneficiário: Thiago Giove Mitsugi
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs