Basonuclin-2 regulates extracellular matrix production and degradation

Epithelial-Mesenchymal Transition (EMT) is essential for tissue patterning and organization. It involves both regulation of cell motility and alterations in the composition and organization of the extracellular matrix (ECM); a complex environment of proteoglycans and fibrous proteins that promotes tissue homeostasis, regulates signaling in response to chemical and biomechanical stimuli and is often dysregulated in diseases such as cancer and fibrosis. Here, we demonstrate that Basonuclin-2 (BNC2), a mesenchymal-expressed gene that has been widely associated with cancer and developmental defects by genome-wide association study (GWAS), is a novel regulator of ECM composition and degradation. We find that at endogenous levels, BNC2 controls the expression of specific collagens, matrix metalloproteases and other matrisomal components in breast cancer cells, and in fibroblasts that are primarily responsible for the deposition and processing of the ECM within the tumour microenvironment. In so doing, BNC2 modulates the motile and invasive properties of cancers which likely explains the association of high BNC2 expression with increasing cancer grade and poor patient prognosis. Comparative gene expression profiling analysis of RNA-seq data for BT549 cells, transfected (in triplicate) with control or BNC2 siRNAs. Gene expression was measured 6 days post-transfection.