Decorin-mediated suppression of tumorigenesis, invasion, and metastasis in inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is a clinically distinct and highly aggressive form of with rapid onset strong propensity to metastasize. The molecular mechanisms underlying the aggressiveness metastatic IBC are largely unknown. Herein, we report that decorin (DCN), small leucine-rich extracellular matrix proteoglycan, downregulated in tumors from patients IBC. Overexpression DCN cells markedly decreased migration, invasion, stem vitro inhibited tumor growth metastasis xenograft mouse models. Mechanistically, functioned as suppressor invasion by destabilizing E-cadherin inhibiting EGFR/ERK signaling. physically binds accelerates its degradation through an autophagy-linked lysosomal pathway. We established inhibits tumorigenesis negatively regulating E-cadherin/EGFR/ERK axis. Our findings offer potential therapeutic strategy for IBC, provide novel mechanism pathobiology.