Cancer cells experience several kinds of stress which they have to overcome or adapt to in order to successfully proliferate and in particular to metastasize. Cell-cycle progression through G1 phase is of particular importance because this is the stage where the decision is made to embark on another cell cycle. A majority of cancer cells are defective in the regulation of the G1/S transition.
We are interested in processes that regulate the progression from G1 into S phase of the cell cycle. We have described a novel G1/S checkpoint that depends on the GCN2 kinase [1]. GCN2 is best known for its important role in the response to nutritional changes such as shortage of amino acids and glucose and is also known to be induced by a number of other stresses that cancer cells experience. Metastasizing cells are particularly vulnerable to these stresses and it has been shown that GCN2 is important for cancer cells to survive and thrive in a hostile microenvironment. Therefore GCN2 is seen as an attractive target for cancer therapy. In addition, it is known to play an important role in neurobiology and is seen as a promising target in the treatment of Alzheimer’s disease.
GCN2 is a known regulator of translation when cells are exposed to stress and we have shown that GCN2 has surprising roles in cell-cycle regulation. Our main interest is to understand the role and regulation of GCN2 further, with regards to both translation regulation and the cell cycle. This knowledge is crucial for knowledge-based therapy of cancer and neurodegenerative diseases.