0000000000718558

AUTHOR

Daniela Grifoni

aPKCζ cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia

Atypical protein kinase C (aPKC) and Lethal giant larvae (Lgl) regulate apical-basal polarity in Drosophila and mammalian epithelia. At the apical domain, aPKC phosphorylates and displaces Lgl that, in turn, maintains aPKC inactive at the basolateral region. The mutual exclusion of these two proteins seems to be crucial for the correct epithelial structure and function. Here we show that a cortical aPKC loading induces Lgl cytoplasmic release and massive overgrowth in Drosophila imaginal epithelia, whereas a cytoplasmic expression does not alter proliferation and epithelial overall structure. As two aPKC isoforms (iota and zeta) exist in humans and we previously showed that Drosophila Lgl i…

research product

The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour suppressor function in vivo

Drosophila lethal giant larvae: (lgl), discs large (dlg) and scribble (scrib) are tumour suppressor genes acting in a common pathway, whose loss of function leads to disruption of cell polarity and tissue architecture, uncontrolled proliferation and growth of neoplastic lesions. Mammalian homologues of these genes are highly conserved and evidence is emerging concerning their role in cell proliferation control and tumorigenesis in humans. Here we investigate the functional conservation between Drosophila lethal giant larvae and its human homologue Hugl-1(Llgl1). We first show that Hugl-1 is lost in human solid malignancies, supporting its role as a tumour suppressor in humans. Hugl-1 expres…

research product