Manchester: The protein kinase C (PKC) family of molecules are enzymes that
facilitate a range of cellular processes, including cell survival,
proliferation, migration and death. In the 1980s it was found that PKCs
were activated by cancer-causing phorbol esters, and led to the
conclusion that PKCs themselves induced the development of tumours.
However, attempts to develop new treatments that prevent tumour cell growth by blocking the activity of PKCs have had little success. A recent study involving Manchester scientists, the findings of which have been published in the journal Cell, has explored the effect of mutations in PKC on tumour growth.
Dr John Brognard, from the Cancer Research UK Manchester Institute at The University of Manchester – part of the Manchester Cancer Research Centre – said: “Despite phorbol esters being known to cause cancers, we’ve seen frustratingly little progress when targeting PKCs to stop tumour growth.”
The Manchester group collaborated with a team from the University of California, San Diego, to analyse PKC mutations in human cancer cells. They found that most were ‘loss of function’ mutations, meaning that the genetic changes stopped PKC from working.
When they corrected these mutations in bowel cancer cells, they saw a reduction in tumour growth, meaning that contrary to our previous understanding, PKC normally acts to block cancer.
“Clinical trials have so far been working on the incorrect assumption that PKC enzymes cause cancer growth. This new insight from our studies has turned current thinking on its head. Looking ahead, instead of blocking PKC activity, new therapies should instead be targeting mechanisms to restore its activity,” added Dr Brognard.
Cancer is one of The University of Manchester’s research beacons - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet.
However, attempts to develop new treatments that prevent tumour cell growth by blocking the activity of PKCs have had little success. A recent study involving Manchester scientists, the findings of which have been published in the journal Cell, has explored the effect of mutations in PKC on tumour growth.
Dr John Brognard, from the Cancer Research UK Manchester Institute at The University of Manchester – part of the Manchester Cancer Research Centre – said: “Despite phorbol esters being known to cause cancers, we’ve seen frustratingly little progress when targeting PKCs to stop tumour growth.”
The Manchester group collaborated with a team from the University of California, San Diego, to analyse PKC mutations in human cancer cells. They found that most were ‘loss of function’ mutations, meaning that the genetic changes stopped PKC from working.
When they corrected these mutations in bowel cancer cells, they saw a reduction in tumour growth, meaning that contrary to our previous understanding, PKC normally acts to block cancer.
“Clinical trials have so far been working on the incorrect assumption that PKC enzymes cause cancer growth. This new insight from our studies has turned current thinking on its head. Looking ahead, instead of blocking PKC activity, new therapies should instead be targeting mechanisms to restore its activity,” added Dr Brognard.
Cancer is one of The University of Manchester’s research beacons - examples of pioneering discoveries, interdisciplinary collaboration and cross-sector partnerships that are tackling some of the biggest questions facing the planet.
Notes for editors
Paper entitled “Cancer-Associated Protein Kinase C Mutations Reveal Kinase’s Role as Tumor Suppressor” Antal CE et al. (2015) Cell.Media enquiries to:
Jamie Brown
Media Relations Officer
The University of Manchester
Tel: 0161 2758383
Email: jamie.brown@manchester.ac.uk