Shutting down elusive cancer pathway might be possible using existing drugs

31 August 2015

Francis Crick Institute researchers have shown in fruit flies that it might be possible to use existing drugs to shut down a protein called Yorkie that is linked to cancer.

Dr Nic Tapon of the Crick (currently based at Lincoln's Inn Fields) said: "About a decade ago, a signal that prevents our cells from forming tumours was discovered. This signal was called the Hippo pathway because it caused fruit flies to grow bigger.

"The Hippo signal works by shutting down a protein called Yorkie, or YAP, in mammals, which is a very potent driver of tissue growth and has been linked to cancer. Currently, many pharmaceutical companies are looking for ways to block Yorkie/YAP activity as a way of treating cancer patients, but this is proving far from easy!"

Another possible pathway for keeping Yorkie in check is via a pathway involving proteins called liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK).

In this study the researchers used sophisticated genetic tools to shut down the Hippo and LKB1/AMPK signals in small groups of cells in fruit flies, mostly in their brains. This allowed them to precisely track the activity of Yorkie and how fast the affected cells grew and divided.

The team found that, in parallel to the Hippo signal, the LKB1/AMPK signal also blocked Yorkie activity.

Dr Tapon said: "This pathway has already been studied intensively in a cancer context, and several drugs are already available. Our study suggests that we may be able to use these drugs, such as Phenformin, in order to shut down Yorkie/YAP.

"However, as we have shown that different fly tissues widely vary in their reliance on the Hippo and LKB1/AMPK signals, we will need to understand how these two signals cooperate in different cell types in humans."

The paper, Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system, is published in the Proceedings of the National Academy of Sciences. 

 

  • A study in fruit flies indicates that it might be possible to use existing drugs to shut down a protein called Yorkie that is linked to cancer.
  • The research was supported by Cancer Research UK, a European Union Marie Curie fellowship and the Francis Crick Institute.