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ERC

SUPERCOMPETITORS — Result In Brief

Project ID: 200130
Funded under: FP7-IDEAS-ERC
Country: Switzerland

Social wars among animal cells

Social wars exist among cells within the bodies of animals to identify suboptimal neighbours and eliminate them. EU funded researchers investigated this phenomenon with significant implications for cancer therapy.
Social wars among animal cells
Cell competition is a type of interaction where more competitive cells replace less competitive cells. The 'battle' between cells is the result of gene mutations that produce cell populations with different proliferation rates. Recent works in the fruit fly (Drosophila) model revealed a role for cell-competition and super-competition in the early stages of cancer formation.

Essentially, cells that acquire a proliferative advantage (winners) grow at the expense of less advantaged cells (losers). The latter die by apoptosis and their corpses are eliminated, while the winners continue growing and eventually spread along the tissue. The EU-funded SUPERCOMPETITORS (Genetic and genomic study of cell competition in Drosophila) research project studied how groups of cells compare their relative fitness levels and decide which cells will remain in the tissue.

New research has revealed that cell competition proceeds through a series of consecutive events. It starts by the mutations that alter cellular fitness in terms of metabolism and proliferation. These differences are then translated by the 'flower code' into cell labels that mark cells as winners or losers. These labels are membrane tags that are products of the Flower gene and give information on the cell status. The molecules that enable cells to recognise this code are still not known.

Loser cells may have upregulation of the protein SPARC (secreted protein acidic and rich in cysteine), which transiently protects them from being eliminated by apoptosis until they accumulate more deficiencies. In the end, loser cells undergo apoptosis and are eliminated from the tissue.

The 'super competitor' hypothesis proposes that tumours outcompete and replace the surrounding tissue by abusing the "flower code" during invasion of healthy organs. In particular, results showed that SPARC is upregulated at the tumour-host boundaries in several types of human cancer.

Imbalances in cell competition could have a role in the early stages of tumour formation, when cells start to overrun the developmental constraints imposed by the genome. These new insights into cell competition will impact our understanding of cancer, regeneration, stem cell biology and ageing.

Related information

Keywords

Cancer, cell competition, Drosophila, SUPERCOMPETITORS, Flower, SPARC
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