Drosophila lethal giant larvae (lgl) is a tumour suppressor gene whose function in
establishing apical-basal cell polarity as well as in exerting proliferation control in epithelial
tissues is conserved between flies and mammals. Individuals bearing lgl null mutations show
a gradual loss of tissue architecture and an extended larval life in which cell proliferation
never ceases and no differentiation occurs, resulting in prepupal lethality. When tissues from
those individuals are transplanted into adult normal recipients, a subset of cells, possibly the
cancer stem cells, are able to proliferate and migrate to distant sites forming metastases which
eventually kill the host. This phenotype closely resembles that of mammalian epithelial
cancers, in which loss of cell polarity is one of the hallmarks of a malignant, metastatic
behaviour associated with poor prognosis. Lgl protein shares with its human counterpart
Human giant larvae-1 (Hugl-1) significant stretches of sequence similarity that we
demonstrated to translate into a complete functional conservation, pointing out a role in cell
proliferation control and tumourigenesis also for the human homologue. The functional
conservation and the power of fly genetics, that allows the researcher to manipulate the fly
genome at a level of precision that exceeds that of any other multicellular genetic system,
make this Drosophila mutant a very suitable model in which to investigate the mechanisms
underlying epithelial tumour formation, progression and metastatisation. In this review, we
will summarise the results obtained in the last years using this model for the study of cancer
biology. Moreover, we will discuss how recent advances in developmental genetics
techniques have succeeded in enhancing the similarities between fly and human
tumourigenesis, giving Drosophila a pivotal role in the study of such a complex genetic
disease.
Keywords: lethal giant larvae, tumour suppressor, Drosophila, Hugl-1, epithelial
cancers, animal model.
