Mechanisms of cell competition.

During our lives, abnormal cells that harbour mutations sporadically arise within normal tissues. Such abnormal cells are normally eliminated to preserve tissue integrity. However, when they are not eliminated, defective cells may over-proliferate and give rise to cancer. A process known as cell competition, originally described in Drosophila, eliminates abnormal and potentially cancerous cells before they can develop into tumours. Cell competition involves poorly understood cellcell interactions between neighbouring cells that result in the elimination of the cells with lower "fitness" (the loser cells), while the fitter cells (the winners) proliferate. Thus, cell competition has a profound impact on cancer development, as it determines whether cancer is prevented by the elimination of abnormal cells or whether abnormal cells can overgrow and form tumours. However, although of fundamental importance, little is known about the molecular mechanisms of cell competition. In this proposal, we aim to get a mechanistic understanding of 1) how cell death is induced in cells that are outcompeted due to the loss of apical-basal polarity, 2) how oncogenic mutations allow abnormal cells to evade cell competition and develop into neoplastic overgrowths, and 3) to identify novel genes that regulate the specification of the winner or loser status during cell competition.

Keywords:Hippo pathway, Apical-basal cell polarity, Loser cell, Winner cell, Cancer, Cell competition

Disciplines:Genetics, Systems biology, Molecular and cell biology