Lack of Glutamine Changes Ribosome Function in Cancer Cell Exosomes

Researchers at the University of Oxford have discovered a new mechanism that enables cancer cells to adapt to their stressors as they grow and respond to therapies. Their findings—published in EMB—demonstrate that cells employ their recycling system to divert reusable proteins and build mutated exosomes. 

Understanding how exosomes developed from endosomes differ from these Rab11a-exosomes is crucial to developing anti-cancer therapies that could be used to support drugs in slowing tumor growth. "These 'bad exosomes' can then give other cells around them a growth-promoting boost and can potentially lead to selection of more aggressive cell types and a worse outcome,” says research leader Deborah Goderdhan. “The production of Rab11a-exosomes may explain why some patients don't respond to certain treatments and why others frequently develop resistance to therapies," she adds. 

The team identified that the release of Rab11a-exosomes from cancer cells increases by the depletion of glutamine, which diverts membrane flux through recycling endosomes. The release is also increased through the reduction of growth regulatory Akt/mTORC1 signalling. 

Although therapy design is part of future research, “developing ways to detect these exosomes in patient blood is an important shorter-term goal,” Goderdhan adds.  “Such an approach might detect cancer at early stages or predict how patients will respond to drugs, both of which could have a major impact on cancer survival and the design of more personalized treatments for patients," she concludes.