TY - JOUR
T1 - Basonuclin-2 regulates extracellular matrix production and degradation
AU - Orang, Ayla
AU - Dredge, B. Kate
AU - Liu, Chi Yau
AU - Bracken, Julie M.
AU - Chen, Chun Hsien
AU - Sourdin, Laura
AU - Whitfield, Holly J.
AU - Lumb, Rachael
AU - Boyle, Sarah T.
AU - Davis, Melissa J.
AU - Samuel, Michael S.
AU - Gregory, Philip A.
AU - Khew-Goodall, Yeesim
AU - Goodall, Gregory J.
AU - Pillman, Katherine A.
AU - Bracken, Cameron P.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - 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.
AB - 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.
KW - Epithelial–mesenchymal transition
KW - tissue patterning
KW - tissue organization
KW - Basonuclin-2
UR - http://www.scopus.com/inward/record.url?scp=85166584494&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/ARC/FT190100544
U2 - 10.26508/lsa.202301984
DO - 10.26508/lsa.202301984
M3 - Article
C2 - 37536977
AN - SCOPUS:85166584494
SN - 2575-1077
VL - 6
JO - Life Science Alliance
JF - Life Science Alliance
IS - 10
M1 - e202301984
ER -