What question did this study set out to answer?

The study investigates how ELK4 influences MBNL1 expression and macrophage infiltration in triple-negative breast cancer to promote tumor progression.

April 13, 2026Open Access

ELK4 transcriptionally represses MBNL1 expression to promote triple-negative breast cancer progression

Puntos clave

The study investigates how ELK4 influences MBNL1 expression and macrophage infiltration in triple-negative breast cancer to promote tumor progression.
Analyzed TNBC dataset GSE38959 for ELK4 expression levels
Performed Transwell, CCK-8, clonal formation, and EdU assays to assess cell behavior
Utilized flow cytometry to detect M2 macrophage infiltration in TNBC patients
Conducted dual-luciferase assays and ChIP-qPCR to study ELK4 and MBNL1 interaction
Performed immunohistochemical staining on TNBC samples to evaluate ELK4 expression and patient prognosis
ELK4 expression was significantly higher in TNBC tissues compared to normal tissues
Increased ELK4 levels correlated with advanced TNM stage and worse prognosis in TNBC patients
ELK4 overexpression enhanced TNBC cell proliferation, migration, and invasion, while knockdown had opposite effects
Macrophage M2 polarization and migration were promoted by conditioned media from ELK4-overexpressing cells
ELK4 was found to repress MBNL1 via binding to its promoter, impacting Notch signaling

Resumen

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Tumor cells often promote the recruitment and infiltration of tumor-associated macrophages (TAMs). We focused on the effect of ETS-like transcription factor 4 (ELK4) on macrophage infiltration in promoting TNBC progression. The publicly available TNBC dataset (GSE38959) was analyzed and found that ELK4 is significantly upregulated in TNBC tissues. Furthermore, Transwell, CCK-8, clonal formation, and EdU assay examined the regulation of ELK4 on cell invasiveness and proliferation. TNBC patient M2 infiltration was detected by flow cytometry. Dual-luciferase assay and ChIP-qPCR experiments were used to assess the bond between ELK4 and Muscleblind Like Splicing Regulator 1 (MBNL1). Analysis of the GSE38959 database indicated that ELK4 expression was upregulated in TNBC. Survival analysis revealed that higher ELK4 expression was associated with poorer prognosis in TNBC patients. Clinically, immunohistochemical staining of ELK4 in 60 TNBC patients’ samples suggested that higher ELK4 expression was associated with advanced TNM stage. Double-immunofluorescence staining for ELK4 and CD68 in TNBC tissues revealed a positive correlation between ELK4 expression and the number of CD68 + M2 macrophages. In vitro experiments, ELK4 overexpression enhanced the proliferation, colony formation, and the migration and invasion ability of TNBC cells. ELK4 knockdown showed opposite effects. Macrophage migration and M2 polarization were promoted when cultured in the conditioned medium derived from ELK4-overexpressing TNBC cells and inhibited in the conditioned medium derived from ELK4-silenced TNBC cells. Furthermore, ELK4 promoted Notch signaling activation in TNBC cells. Notably, ELK4 bound to the MBNL1 promoter and downregulated its activity, which was confirmed via dual-luciferase reporter assay and ChIP-qPCR. Taken together, our results demonstrate that ELK4 may affect the Notch1 signaling pathway and promote macrophage M2 infiltration through transcriptional inhibition of MBNL1, ultimately promoting TNBC development.

Me gusta

Guardar

Ver artículo completo