Scientists discover inner-workings of key protein which causes bowel cancer
Scientists have revealed the inner workings of a key protein involved in bowel cancer, paving the way for new drugs to treat the disease.
The tankyrase protein is involved in a wide range of processes in the cell, which means it could lead to better and less toxic cancer drugs, researchers suggest. Using Nobel Prizewinning techniques, scientists foundhowtheproteinswitches itself on and off by self-assembling into 3D chain-like structures. The elusive but importantproteinplaysaparticularly important role in helping drive bowel cancer.
Scientists at The Institute of Cancer Research, London (Icr),believetheirresearchwill open the door to new types of cancer treatment that can control tankyrase more precisely than is currently possible, with fewer side effects.
Study leader Professor Sebastian Guettler, deputy head of the division of Structural Biology at the ICR said: "Our study has provided vital new information about a particular protein molecule called tankyrase, which plays an important role in bowel cancer and other diseases but has so far eluded our understanding.
"We're playing catch up - we have all these drugs to block tankyrasebeingcreated,butwe don't have enough basic understanding to use them as treatments. We have shown how tankyrase is switched on and can go from a 'lazy' enzyme to an active one.
"If we can create better less toxic drugs to control this process, we could pave the way for an effective bowel cancer treatment in the future."
Accordingtothefindingspublishedinnature,thefundamental discovery could have implications for treating various cancers, as well as diabetes and inflammatory,cardiacandneurodegenerative diseases.
Professorkristianhelin,chief executiveoftheicr,said:"these fundamental findings help us understand how the extremely important tankyrase protein works within cells. Almost all bowelcancershavehyperactive
Wnt-signalling that operates through tankyrase, and they could therefore potentially be treated with drugs targeting it.
"I am hopeful these key advances in our understanding of tankyrase will help us overcome the limitations of currently available drug candidates - hopefully bringing us a step closer to a new targeted bowel cancer treatment.
"Tankyrase is also responsible for regulating a wide range of processes relevant to a varietyofdiseases,notjustcancer,so this research could have broad implications."
In the past ten years, scientists have developed drugs to block tankyrase in an attempt totreatbowelcancer-butofthe complexity of the processes it is involved in, the drugs led to too many side effects for them to reach clinical trials. To really understand how tankyrase inhibitors work and how to develop less toxic treatments, scientists at the ICR set out to discover new structural informationusingcutting-edgecryoelectron microscopy.
This extremely powerful type of microscopy freezes samples at -180°C to enable minute details of protein shape to be imaged.
This allowed them to visualise and capture how tankyrase 'self-assembles' into fibres - chain-like structures - and why fibre formation is needed for tankyrase to activate itself.