aPKCzeta 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 is the functional homologue of the Human giant larvae-1 (Hugl-1) protein, we argued if the same mechanism of mutual exclusion could be impaired in human epithelial disorders and investigated aPKCiota, aPKCzeta and Hugl-1 localization in cancers deriving from ovarian surface epithelium. Both in mucinous and serous histotypes, aPKCzeta showed an apical-to-cortical redistribution and Hugl-1 showed a membrane-to-cytoplasm release, perfectly recapitulating the Drosophila model. Although several recent works support a causative role for aPKCiota overexpression in human carcinomas, our results suggest a key role for aPKCzeta in apical-basal polarity loosening, a mechanism that seems to be driven by changes in protein localization rather than in protein abundance.
Grifoni
D
D
Dipartimento di Biologia Evoluzionistica Sperimentale, Alma Mater Studiorum, Via Selmi 3, 40126 Bologna, Italy. daniela.grifoni@unibo.it
Garoia
F
F
Bellosta
P
P
Parisi
F
F
De Biase
D
D
Collina
G
G
Strand
D
D
Cavicchi
S
S
Pession
A
A
D000818:Animals; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014921:Wings, Animal / Q000196:embryology; D000099221:Protein Kinase C zeta
D029721:Drosophila Proteins; D011493:Protein Kinase C; D025521:Tumor Suppressor Proteins; D000099221:Protein Kinase C zeta; C081435:l(2)gl protein, Drosophila; C115015:PKC-3 protein