Cancer cells grow and divide in an uncontrolled manner. A new study now shows how alterations in a cell's degradation hubs, called lysosomes, can cause abnormal cell growth. The results are published in the scientific journal Nature Communications.
Normal cells have several control mechanisms that prevent them from growing uncontrollably. During the last few years, it has become increasingly clear that these regulatory processes are taking place on the surface of lysosomes, which are small membrane-encapsulated vesicles that function as degradation centres of all cells. A cell can have hundreds of lysosomes that are organised into complex networks. Cancer cells frequently have alterations in the organisation of their lysosome networks, although it remains unclear to what degree this contributes to tumor progression.
In the present study, scientists, have found that the amount of lysosomes in a lysosomal network affects cellular growth through the activation of a protein called mTOR.
"We saw that when the number of lysosomes increased, mTOR molecules on the lysosomal surface became hyperactivated. Since mTOR is a central stimulator of cellular growth, this leads to increased growth, says the study lead.
The scientists have also identified another protein, Rap1, that regulates both the number of lysosomes present in the lysosomal network, and its organization.
When amino acids are limited, the Rap1-GTPases confine lysosomes to the perinuclear region and reduce lysosome abundance, which suppresses mTORC1 signaling. Rap1 activation, which is independent of known amino acid signaling factors, limits the lysosomal surface available for mTORC1 activation. Conversely, Rap1 depletion expands the lysosome population, which markedly increases association between mTORC1 and its lysosome-borne activators, leading to mTORC1 hyperactivity.
"Although this study is in an early phase, it demonstrates that lysosomes play a central role in cellular growth control. We need more knowledge about how changes in a lysosomal network contribute to cancer, which is something we are about to test in models of human cancers," says the author.
Lysosomal alterations can lead to cancer
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