NUMERO: #20250041

Título: THERAPEUTIC TARGETING OF E2F IN SALIVARY GLAND MUCOEPIDERMOID CARCINOMA REDUCES CANCER STEM CELLS

Nome do Apresentador: Jaqueline Vaz VANINI

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Patologia Oral

Resumo: Background: The E2F family of transcription factors plays critical roles in cell cycle regulation and other important cell processes. While the E2F pathway is often altered in various cancers, its role in salivary gland cancer remains underexplored. E2F also regulates Bmi-1, a protein linked to cancer stem cell self-renewal, making it a potential therapeutic target.

Objective: This study evaluates the impact of E2F inhibition on Bmi-1 expression and cancer stemness in salivary gland mucoepidermoid carcinoma (MEC).

Study design: Three MEC cell lines were treated with HLM006474, a pan-E2F inhibitor. Western blot analysis assessed the expression of E2F, Bmi-1, and related proteins. Flow cytometry staining for ALDH and CD44 quantified cancer stem cells, and propidium iodide staining analyzed cell cycle. Sphere formation assays evaluated stem cell self-renewal.

Results: HLM006474 treatment reduced Bmi-1 expression, induced tumor suppressors p53 and p21, and decreased the cancer stem cell population in a dose-dependent manner. Additionally, sphere formation was significantly reduced.

Conclusion: E2F inhibition effectively reduces the cancer stem cell population in preclinical MEC models. If confirmed in vivo, targeting E2F could offer a promising therapeutic strategy for patients with this type of cancer.

Funding: CNPq 200210/2022-0 (JVV) and NIH/NIDCR R01-DE21139 (JEN).

Autor 1:  Jaqueline Vaz VANINI

E-mail 1:  [email protected]

Autor 2:   José Martins FIGUEREDO JR.

E-mail 2:  [email protected]

Autor 3 :  Fabio Daumas NUNES

E-mail 3:  [email protected]

Autor 4:  Jacques E. NOR

E-mail 4:  [email protected]