Researchers at University of York's Jack Birch Unit have revealed how direct communication between cells can help maintain healthy human tissue - potentially paving the way for new treatments for bladder cancer.
Dr Hinley inspects the cells through the microscope.
Funded by York Against Cancer and published in the journal Life Science Alliance, the study focused on cells from the urothelium, the specialised lining of the human urinary tract, acting as an effective barrier that protects the body from the toxins present in urine.
The urothelium also possesses the ability to repair itself after injury, and by studying a protein called Connexin 32 (Cx32) the researchers were able to learn more about how this is achieved.
Cx32 is a protein which forms channels between cells, linking them together and allowing cells to communicate by passing molecular messages from cell to cell. To understand Cx32's function in the urothelium, the team experimentally blocked its communication channels between cells. The study showed that this did not damage the urothelium or interfere with normal cell specialisation. It did, however, trigger a dramatic shift in behaviour.
The team from the Jack Birch unit showed that while blocking Cx32 channels did not disrupt the strong barrier abilities of the urothelium, it did cause cells to become more mobile and activate behaviours commonly linked to cancer spread.
Suppressed communication
When Cx32 communication was suppressed, the cells began acting as though they were repairing a wound. While such responses are useful after an injury, they can be harmful when activated inappropriately.
Dr Jenny Hinley, lead author of the study, said: "When we then studied a group of aggressive bladder (urothelial) cancers, we found that patterns of Cx32 protein were informative for understanding tumour behaviour. Tumours with misdirected patterns of Cx32 expression showed evidence of rapid growth and displayed more invasive characteristics than cancers with normal Cx32".
The findings suggest that Cx32-mediated cell communication plays a protective role by keeping urothelial cells in a stable state. Loss or misplacement of Cx32 may remove this stable state, allowing cells linked to tumour growth and metastasis to grow unhindered.
The findings of this research indicate that the patterns of Cx32 protein in tumours may be useful to clinicians in identifying patients with more aggressive tumours that require alternative treatment strategies and could help identify new treatments.
Further information:
York Against Cancer funded both Jenny Hinley's PhD studentship and the subsequent research which led to the findings in this publication, under the directorship of Professor Jenny Southgate.
Hinley, J. et al. 2026. Connexin 32 constrains a mesenchymal-like switch in differentiated 2 urothelium and luminal cancers. Life Science Alliance. Vol. 9. Issue 5.
