A group of scientists at the Instituto Gulbenkian de Cincia, in Portugal, have uncovered a surprising link between the cell's skeleton and organ size. The team, led by Florence Janody, show in the journal Development(*), that one of the proteins that regulates the skeleton of the cell also acts to blocks activation of genes that promote cell survival and proliferation. Their findings have implications for cancer research, as they add to the puzzle of understanding how proliferation genes are abnormally activated, often leading to tumours.
During development of an embryo, cells proliferate and organs grow. This process is tightly regulated, at several levels, to ensure that organs do not outgrow the body they are in. One of the key regulators in this process is the Hippo complex of proteins - first identified in the fruit fly Drosophila melanogaster. Mutant flies, in which this complex is defective are larger than their counterparts - they are hippopotamus-like. A search for analogous genes uncovered a similar role for the Hippo complex in mammals - organs grow larger than they should. In adults, this abnormal and untimely growth often leads to tumour formation.
A flurry of papers has shown that the Hippo complex itself is regulated by a range of signaling inputs within the cell. Florence Janody's group identified a new, and unexpected input: the cell skeleton (called cytoskeleton), in particular one of its proteins, the actin-capping protein.
Using Drosophila larvae, the IGC team showed that when the actin-capping proteins are inactive, there is overgrowth of tissue in the area that will become the adult wing. This growth is reminiscent of tumour formation. The researchers dissected the different steps in the process that lead to abnormal growth. Inactivating actin-capping proteins leads to accumulation of actin, a major component of the cytoskeleton; this reduces the activity of the Hippo complex, leaving another protein, Y
|Contact: Ana Godinho|
Instituto Gulbenkian de Ciencia