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

Oncogene volume 26, pages 5960–5965 (2007)Cite this article

Abstract

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 (ι and ζ) 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 aPKCι, aPKCζ and Hugl-1 localization in cancers deriving from ovarian surface epithelium. Both in mucinous and serous histotypes, aPKCζ 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 aPKCι overexpression in human carcinomas, our results suggest a key role for aPKCζ in apical–basal polarity loosening, a mechanism that seems to be driven by changes in protein localization rather than in protein abundance.

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Acknowledgements

We thank all members of the ‘TNT Group’ for fraternal support, Raffaella Buda and Guglielmo Caruso for tumor samples and Chris Doe for UAS-aPKC strains. FG is supported by a fellowship from ‘Fondazione Cassa di Risparmio in Bologna’, FP is supported by a fellowship from the PhD program in ‘Cell Biology and Physiology’ of the University of Bologna.

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Author notes

  1. D Grifoni and F Garoia: These two authors contributed equally to this work.

Authors and Affiliations

  1. Dipartimento di Biologia Evoluzionistica Sperimentale, Alma Mater Studiorum, Bologna, Italy

    D Grifoni, F Garoia, F Parisi & S Cavicchi

  2. Dipartimento di Patologia Sperimentale, Alma Mater Studiorum, Bologna, Italy

    D Grifoni & A Pession

  3. Biology Department, City College of New York – CUNY, New York, NY, USA

    P Bellosta

  4. Alma Mater Studiorum, Sezione di Anatomia Patologica, Ospedale Bellaria, Bologna, Italy

    D De Biase, G Collina & A Pession

  5. First Department of Internal Medicine, Johannes Gutenberg University, Mainz, Germany

    D Strand

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  1. D Grifoni
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Correspondence to D Grifoni.

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Grifoni, D., Garoia, F., Bellosta, P. et al. aPKCζ cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia. Oncogene 26, 5960–5965 (2007). https://doi.org/10.1038/sj.onc.1210389

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