Targeting HMGA1 contributes to immunotherapy in aggressive breast cancer while suppressing EMT

Abstract

Metastasis is an obstacle to the clinical treatment of aggressive breast cancer (BC). Studies have shown that high mobility group A1 (HMGA1) is abnormally expressed in various cancers and mediates tumor proliferation and metastasis. Here, we provided more evidence that HMGA1 mediated epithelial to mesenchymal transition (EMT) through the Wnt/β-catenin pathway in aggressive BC. More importantly, HMGA1 knockdown enhanced antitumor immunity and improved the response to immune checkpoint blockade (ICB) therapy by upregulating programmed cell death ligand 1 (PD-L1) expression. Simultaneously, we revealed a novel mechanism by which HMGA1 and PD-L1 were regulated by the PD-L1/HMGA1/Wnt/β-catenin negative feedback loop in aggressive BC. Taken together, we believe that HMGA1 can serve as a target for the dual role of anti-metastasis and enhancing immunotherapeutic responses.

Keywords: Aggressive breast cancer; Antitumor immunity; HMGA1; Metastases; PD-L1.