Connexin 32 constrains a mesenchymal-like switch in differentiated urothelium and luminal cancers.
No Thumbnail Available
All Authors
Hinley, J.
Baker, SC.
Mason, AS.
Kyriazis, G.
Masood, O.
Southgate, J.
LTHT Author
Masood, Omar
LTHT Department
Abdominal Medicine & Surgery
Renal Medicine
Renal Medicine
Non Medic
Publication Date
2026
Item Type
Journal Article
Language
Subject
HUMANS , HOSPITALISATION , URINARY BLADDER NEOPLASMS , CELL DIFFERENTIATION , SIGNAL TRANSDUCTION , CELL COMMUNICATION , CELL PHYSIOLOGICAL PHENOMENA
Subject Headings
Abstract
The molecular programming of epithelial wound repair provides the origin for the signalling pathways that drive the growth and spread of carcinoma cells. Urothelium is the mitotically quiescent, barrier-forming transitional epithelium of the urinary tract, characterised by uniquely specialised superficial cells and a remarkable regenerative capacity in response to damage. Connexin 32 (Cx32) was expressed by differentiated human urothelium where it predominantly localised to the basolateral borders of superficial urothelial cells. Suppression of Cx32 gap junction intercellular communication did not affect differentiation but instigated the switch to a highly migratory, wound healing phenotype marked by TGFbeta-SMAD signalling, ECM-remodelling, and induction of mesenchymal and cell-cycle markers. Immunohistological classification of muscle-invasive bladder cancers revealed Cx32 expression to be informative in luminal tumour biology, with non-membrane localised Cx32 defining a Ki67-high, vimentin-expressing, and TGFbeta-activated subset of luminal tumours. Our findings identify Cx32 cell-cell communication as suppressing migratory and proliferative behaviours in normal urothelial differentiation and suggest that Cx32 assessment, within the context of luminal muscle-invasive bladder cancer, can predict more invasive biology. This reveals the potential for differentiated cancers to exhibit EMT.
Journal
Life Science Alliance