ECM1 is associated with endocrine resistance in ER+ breast cancers.

Abstract

Extracellular matrix protein 1 (ECM1) is associated with a poor prognosis of breast cancers. However, the role of ECM1 with endocrine resistance in estrogen receptor-positive (ER⁺) breast cancers has not been elucidated yet. We show that ECM1 promotes endocrine resistance in ER⁺ breast cancers. ECM1 is overexpressed in luminal breast cancer patients compared to the basal type of breast cancer. Significantly, higher expression of ECM1 is associated with poor response to endocrine therapies in luminal B breast cancer patients. We found that ECM1 is upregulated in CAMA1 and MDA-MB-361 cells grown in long-term estrogen-deprived (LTED) conditions. Moreover, the ablation of ECM1 significantly inhibited the proliferation of CAMA1 LTED and MDA-MB-361 LTED cells. Finally, an interrogation of a dataset containing transcriptome and proteome of breast cancer cell lines revealed that the level of ECM1 mRNA is positively correlated with that of phosphorylated Src. Based on these findings, we strongly suggest that ECM1 significantly contributes to the acquisition of endocrine resistance in ER⁺ breast cancers by the activation of Src.