DLK1 Is Associated with Stemness Phenotype in Medullary Thyroid Carcinoma Cell Lines

Autor(es)

da Silva, Danilo Dias ; Araldi, Rodrigo Pinheiro ; Belizario, Mariana Rocha ; Rocha, Welbert Gomes ; Maciel, Rui Monteiro de Barros ; Cerutti, Janete Maria

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 22, p. 19-pg., 2024-11-01.

Resumo

Medullary thyroid carcinoma (MTC) is a rare and aggressive tumor, often requiring systemic treatment in advanced or metastatic stages, where drug resistance presents a significant challenge. Given the role of cancer stem cells (CSCs) in cancer recurrence and drug resistance, we aimed to identify CSC subpopulations within two MTC cell lines harboring pathogenic variants in the two most common MEN2-associated codons. We analyzed 15 stemness-associated markers, along with well-established thyroid stem cell markers (CD133, CD44, and ALDH1), a novel candidate (DLK1), and multidrug resistance proteins (MRP1 and MRP3). The ability to efflux the fluorescent dye Hoechst 3342 and form spheroids, representing CSC behavior, was also assessed. MZ-CRC-1 cells (p.M918T) displayed higher expressions of canonical markers, DLK1, and MRP proteins than TT cells (p.C634W). MZ-CRC-1 cells also formed more spheroids and showed less dye accumulation (p < 0.0001). Finally, we observed that DLK1+ cells (those expressing DLK1) in both cell lines exhibited significantly higher levels of stemness markers compared to DLK1- cells (those lacking DLK1 expression). These findings underscore DLK1's role in enhancing the stemness phenotype, providing valuable insights into MTC progression and resistance and suggesting potential therapeutic implications. (AU)

• Processo FAPESP: 23/16471-4 - Edição gênica de DLK1 por CRISPR/Cas9 em linhagens celulares derivadas de carcinoma medular e diferenciado de tireoide humana
• Beneficiário: Mariana Rocha Belizario
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/02752-6 - Neoplasia Endócrina múltipla tipo 2 e Carcinoma Medular da Tiroide: novas questões da biologia do desenvolvimento, genética, imunologia, epidemiologia, mecanismo de doença e manejo clínico
• Beneficiário: Rui Monteiro de Barros Maciel
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 22/16827-0 - Avaliação da cooperação entre variantes nos genes RAS e HIPK2 na gênese e progressão do Câncer diferenciado de tiroide
• Beneficiário: Welbert Gomes Rocha
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 22/09713-9 - Identificação de genes de predisposição ao desenvolvimento do Câncer de Tiroide Familial Não-Medular por sequenciamento completo do exoma
• Beneficiário: Janete Maria Cerutti
• Modalidade de apoio: Auxílio à Pesquisa - Regular