System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells.

ABSTRACT: Estrogen receptor-positive breast cancer (ER+BC) accounts for ∼70% of all breast tumors, and 20%-40% of patients develop metastases. Everolimus is an mammalian target of rapamycin (mTOR) inhibitor used in combination with exemestane for metastatic ER+BC. However, resistance remains common and leads to poor survival outcomes. To uncover resistance mechanisms, we analyze transcriptomic profiles from everolimus-sensitive and -resistant ER+BC cell lines. Our study uncovers persistent activation of a growth-factor signaling meta-phenotype in resistant cells involving IGF1R, ESR1, and mitogen-activated protein kinase (MAPK) pathways. We identify SMARCD3 regulons linked to this meta-phenotype. Additionally, we find SMARCD3 regulon activity elevated in everolimus-refractory patient tumors. Importa

SUBMITTER: Medina EF 

PROVIDER: S-EPMC12711665 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature