FOXA1 promotes SCLC chemoresistance [RNA-Seq]

While chemotherapy has been the cornerstone of first-line treatment, most SCLC patients develop chemoresistance shortly after an initial response, and the molecular basis of this resistance remains poorly understood. Here, we identify FOXA1 as a frequently amplified and upregulated gene in SCLC, with high FOXA1 expression correlating with poor outcomes.

We further demonstrate that FOXA1 overexpression promotes resistance to chemotherapy. Mechanistically, we reveal that WNT5A is a downstream target of FOXA1 that mediates chemoresistance through activation of the Wnt/β-catenin pathway. FOXA1 also induces epithelial-mesenchymal transition (EMT) in SCLC cells, and human SCLC tumors with high FOXA1 expression exhibit enriched EMT and Wnt/β-catenin pathway signatures.