Basonuclin-2 regulates extracellular matrix production and degradation

Ayla Orang, B. Kate Dredge, Chi Yau Liu, Julie M. Bracken, Chun Hsien Chen, Laura Sourdin, Holly J. Whitfield, Rachael Lumb, Sarah T. Boyle, Melissa J. Davis, Michael S. Samuel, Philip A. Gregory, Yeesim Khew-Goodall, Gregory J. Goodall, Katherine A. Pillman, Cameron P. Bracken

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Abstract

Epithelial-mesenchymal transition is essential for tissue patterning and organization. It involves both regulation of cell motility and alterations in the composition and organization of the ECM-a complex environment of proteoglycans and fibrous proteins essential for tissue homeostasis, signaling in response to chemical and biomechanical stimuli, and is often dysregulated under conditions such as cancer, fibrosis, and chronic wounds. Here, we demonstrate that basonuclin-2 (BNC2), a mesenchymal-expressed gene, that is, strongly associated with cancer and developmental defects across genome-wide association studies, 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 production 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.

Original languageEnglish
Article numbere202301984
Number of pages17
JournalLife Science Alliance
Volume6
Issue number10
Early online date3 Aug 2023
DOIs
Publication statusPublished - 1 Oct 2023
Externally publishedYes

Keywords

  • Epithelial–mesenchymal transition
  • tissue patterning
  • tissue organization
  • Basonuclin-2

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