Autophagy insights could help in quest for new cancer therapies

17 December 2015

Francis Crick Institute scientists have discovered how two molecules regulate autophagy - a recycling process used by cells to maintain their health by removing harmful substances and to aid survival under stresses including starvation. 

The findings have possible implications for developing new treatments for cancer.

Dr Sharon Tooze of the Crick (currently based at Lincoln's Inn Fields) said: "In healthy cells autophagy is good for cells and helps them perform their normal functions. However in cancer cells, autophagy can be hijacked to allow cancer cells to survive under adverse conditions. Understanding how autophagy can be controlled will benefit human health by providing ways to control autophagy in cancer cells, and hopefully kill cancer cells."

Microscope images show groups of cells, with molecules in the cells labelled with florescent dyes. In the presence of WAC (left), GABARAP (red) participates in autophagy and is away from GM130 (green). Without WAC (right), GABARAP (red) is stuck on GM130 (green) – this is shown in yellow – and GABARAP no longer participates in autophagy.

Microscope images show groups of cells, with molecules in the cells labelled with florescent dyes. In the presence of WAC (left), GABARAP (red) participates in autophagy and is away from GM130 (green). Without WAC (right), GABARAP (red) is stuck on GM130 (green) – this is shown in yellow – and GABARAP no longer participates in autophagy. (Click to view larger image)

WAC was discovered as a new molecule regulating autophagy that binds to GM130, a molecule previously implicated in cancer. WAC stops GM130 binding to a key autophagy molecule called GABARAP, which allows GABARAP to move into the right place in the cell at the right time for autophagy to occur.

The process involves controlling a collection of GABARAP molecules at the centrosome - a structure near the centre of our cells that is a 'master controller' of many important cellular activities such as cell division and differentiation, and the conversion of one cell type into another.

Dr Tooze said: "Abnormal centrosome structure and number has been linked with cancer and other diseases.

"Our work provides a link between this essential autophagy molecule, GABARAP, and the centrosome, and importantly implies that the regulation of autophagy could be linked to the control of cell division, growth and differentiation.

"The study's findings could provide a new avenue for therapies affecting cell survival and tumour growth."

The paper, Activation of ULK Kinase and Autophagy by GABARAP Trafficking from the Centrosome Is Regulated by WAC and GM130, is published in Molecular Cell.

  • Autophagy is a recycling process used by cells to maintain their health by removing harmful substances and to aid survival under stresses including starvation.
  • Francis Crick Institute scientists have discovered how two molecules regulate autophagy - with possible implications for developing cancer treatments.
  • Funding was provided by Cancer Research UK and the Francis Crick Institute.