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A tumor microenvironment-driven network regulated by STAT3 and p65 controls the enrichment of cancer stem cells in human HR+/HER2- breast cancer cells

ABSTRACT: The high incidence of the HR+/HER2- breast cancer subtype is a major public health concern, leading us to explore the way three arms of the tumor microenvironment (TME) – hormonal, inflammatory and growth-stimulating – affect tumor progression in this disease. Our past findings indicate that such a joint “TME Stimulation” induces pro-metastatic traits in HR+/HER2- cells, primarily enrichment of cancer stem cells (CSCs), playing key roles in metastasis in vivo. Here, we reveal unexpected roles for STAT3 in this setting, serving as negative regulator that limits CSC enrichment while promoting cancer cell abilities to exploit the immune/inflammatory system in their favor. Moreover, our data provide evidence to novel roles for the strong pro-inflammatory transcription factor p65, whose activities could compensate for complete loss of STAT3 and recapitulate its ability to limit CSC enrichment. These findings call for in depth studies on STAT3 and p65 roles in regulating TME activities in malignant diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE226339 | GEO | 2023/04/19

REPOSITORIES: GEO

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