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Polarity proteins in migration and invasion

Oncogene volume 27, pages 6970–6980 (2008)Cite this article

Abstract

Cancer is the result of the deregulation of cell proliferation and cell migration. In advanced tumors, cells invade the surrounding tissue and eventually form metastases. This is particularly evident in carcinomas in which epithelial cells have undergone epithelial–mesenchymal transition. Increased cell migration often correlates with a weakening of intercellular interactions. Junctions between neighboring epithelial cells are required to establish and maintain baso-apical polarity, suggesting that not only loss of cell–cell adhesion but also alteration of cell polarity is involved during invasion. Accordingly, perturbation of cell polarity is an important hallmark of advanced invasive tumors. Cell polarity is also essential for cell migration. Indeed, a front-rear polarity axis has first to be generated to allow a cell to migrate. Because cells migrate during invasion, cell polarity is not completely lost. Instead, polarity is modified. From a nonmigrating baso-apically polarized epithelial phenotype, cells acquire a polarized migrating mesenchymal phenotype. The aim of this review is to highlight the molecular relationship between the control of cell polarity and the regulation of cell motility during oncogenesis.

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Abbreviations

APC:

adenomatous polyposis coli

aPKC:

atypical protein kinase C

Dvl:

disheveled

EMT:

epithelial–mesenchymal transition

References

  • Abdelilah-Seyfried S, Cox DN, Jan YN . (2003). Bazzooka is a permissive factor for the invasive behavior of discs large tumor cells in Drosophila ovarian follicular epithelia. Development 130: 1927–1935.

    Article  CAS  PubMed  Google Scholar 

  • Alessi DR, Sakamoto K, Bayascas JR . (2006). LKB1-dependent signaling pathways. Annu Rev Biochem 75: 137–163.

    Article  CAS  PubMed  Google Scholar 

  • Allen WE, Zicha D, Ridley AJ, Jones GE . (1998). A role for Cdc42 in macrophage chemotaxis. J Cell Biol 141: 1147–1157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aranda V, Nolan ME, Muthuswamy SK . (2008). Par complex in cancer: a regulator of normal cell polarity joins the dark side. Oncogene 27: 6878–6887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arquier N, Perrin L, Manfruelli P, Semeriva M . (2001). The Drosophila tumor suppressor gene lethal(2)giant larvae is required for the emission of the Decapentaplegic signal. Development 128: 2209–2220.

    Article  CAS  PubMed  Google Scholar 

  • Assemat E, Bazellieres E, Pallesi-Pocachard E, Le Bivic A, Massey-Harroche D . (2008). Polarity complex proteins. Biochim Biophys Acta 1778: 614–630.

    Article  CAS  PubMed  Google Scholar 

  • Baas A, Kuipers J, van der Wel NN, Batlle E, Koerten HK, Peters PJ et al. (2004). Complete polarization of single intestinal cell upon activation of LKB1 by STRAD. Cell 116: 457–466.

    Article  CAS  PubMed  Google Scholar 

  • Barnes AP, Lilley BN, Pan YA, Plummer LJ, Powell AW, Raines AN et al. (2007). LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons. Cell 129: 549–563.

    Article  CAS  PubMed  Google Scholar 

  • Barth AI, Caro-Gonzalez HY, Nelson WJ . (2008). Role of adenomatous polyposis coli (APC) and microtubules in directional cell migration and neuronal polarization. Semin Cell Dev Biol 19: 245–251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME et al. (2001). Transforming growth factor-b1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol Biol Cell 12: 27–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bilder D, Li M, Perrimon N . (2000). Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289: 113–116.

    Article  CAS  PubMed  Google Scholar 

  • Bilder D, Schober M, Perrimon N . (2003). Integrated activity of PDZ complexes regulates epithelial polarity. Nat Cell Biol 5: 53–58.

    Article  CAS  PubMed  Google Scholar 

  • Cau J, Hall A . (2005). Cdc42 controls the polarity of the actin and microtubule cytoskeletons through two distinct signal transduction pathways. J Cell Sci 118: 2579–2587.

    Article  CAS  PubMed  Google Scholar 

  • Cavallaro U, Christofori G . (2004). Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann N Y Acad Sci 1014: 58–66.

    Article  CAS  PubMed  Google Scholar 

  • Cavatorta AL, Fumero G, Chouhy D, Aguirre R, Nocito AL, Giri AA et al. (2004). Differential expression of the human homologue of Drosophila discs large oncosuppressor in histologic samples from human papillomavirus-associated lesions as a marker for progression to malignancy. Int J Cancer 111: 373–380.

    Article  CAS  PubMed  Google Scholar 

  • Charest PG, Firtel RA . (2007). Big roles for small GTPases in the control of directed cell movement. Biochem J 401: 377–390.

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Macara IG . (2005). Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nat Cell Biol 7: 262–269.

    Article  CAS  PubMed  Google Scholar 

  • Cohen EE, Lingen MW, Zhu B, Zhu H, Straza MW, Pierce C et al. (2006). Protein kinase C zeta mediates epidermal growth factor-induced growth of head and neck tumor cells by regulating mitogen-activated protein kinase. Cancer Res 66: 6296–6303.

    Article  CAS  PubMed  Google Scholar 

  • Dhillon AS, Hagan S, Rath O, kolch W . (2007). MAP kinase signalling pathways in cancer. Oncogene 26: 3279–3290.

    Article  CAS  PubMed  Google Scholar 

  • Dow LE, Elsum IA, King CL, Kinross KM, Richardson HE, Humbert PO . (2008). Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling. Oncogene, e-pub ahead of print 21 July 2008.

  • Dow LE, Humbert PO . (2007). Polarity regulators and the control of epithelial architecture, cell migration, and tumorigenesis. Int Rev Cytol 262: 253–302.

    Article  CAS  PubMed  Google Scholar 

  • Dow LE, Kauffman JS, Caddy J, Peterson AS, Jane SMR, Russell SM et al. (2007). The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene 26: 2272–2282.

    Article  CAS  PubMed  Google Scholar 

  • Eder AM, Sui X, Rosen DG, Nolden LK, Cheng KW, Lahad JP et al. (2005). Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA 102: 12519–12524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Etienne-Manneville S . (2004a). Actin and microtubules in cell motility: which one is in control? Traffic 5: 470–477.

    Article  CAS  PubMed  Google Scholar 

  • Etienne-Manneville S . (2004b). Cdc42—the centre of polarity. J Cell Sci 117: 1291–1300.

    Article  CAS  PubMed  Google Scholar 

  • Etienne-Manneville S, Hall A . (2001). Integrin-mediated Cdc42 activation controls cell polarity in migrating astrocytes through PKCζ. Cell 106: 489–498.

    Article  CAS  PubMed  Google Scholar 

  • Etienne-Manneville S, Hall A . (2002). Rho GTPases in cell biology. Nature 420: 629–635.

    Article  CAS  PubMed  Google Scholar 

  • Etienne-Manneville S, Hall A . (2003). Cdc42 regulates GSK3 and adenomatous polyposis coli (APC) to control cell polarity. Nature 421: 753–756.

    Article  CAS  PubMed  Google Scholar 

  • Etienne-Manneville S, Manneville JB, Nicholls S, Ferenczi M, Hall A . (2005). Cdc42 and Par6-PKCζ regulate the spatially localized association of Dlg1 and APC to control cell polarization. J Cell Biol 170: 895–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Forcet C, Etienne-Manneville S, Gaude H, Fournier L, Debilly S, Salmi M et al. (2005). Functional analysis of Peutz–Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity. Hum Mol Genet 14: 1283–1292.

    Article  CAS  PubMed  Google Scholar 

  • Friedl P . (2004). Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 16: 14–23.

    Article  CAS  PubMed  Google Scholar 

  • Friedl P, Wolf K . (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3: 362–374.

    Article  CAS  PubMed  Google Scholar 

  • Gardiol D, Zacchi A, Petrera F, Stanta G, Banks L . (2006). Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression. Int J Cancer 119: 1285–1290.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein B, Macara IG . (2007). The PAR proteins: fundamental players in animal cell polarization. Dev Cell 13: 609–622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes ER, Jani S, Gundersen GG . (2005). Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121: 451–463.

    Article  CAS  PubMed  Google Scholar 

  • Goode S, Perrimon N . (1997). Inhibition of patterned cell shape change and cell invasion by Discs large during Drosophila oogenesis. Genes Dev 11: 2532–2544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guarino M . (2007). Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol 39: 2153–2160.

    Article  CAS  PubMed  Google Scholar 

  • Helfrich I, Schmitz A, Zigrino P, Michels C, Haase I, le Bivic A et al. (2007). Role of aPKC isoforms and their binding partners Par3 and Par6 in epidermal barrier formation. J Invest Dermatol 127: 782–791.

    Article  CAS  PubMed  Google Scholar 

  • Hemminki A . (1999). The molecular basis and clinical aspects of Peutz-Jeghers syndrome. Cell Mol Life Sci 55: 735–750.

    Article  CAS  PubMed  Google Scholar 

  • Hirohashi S . (1998). Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153: 333–339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang H, He X . (2008). Wnt/beta-catenin signaling: new (and old) players and new insights. Curr Opin Cell Biol 20: 119–125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Humbert PO, Dow LE, Russell SM . (2006). The Scribble and Par complexes in polarity and migration: friends or foes? Trends Cell Biol 16: 622–630.

    Article  CAS  PubMed  Google Scholar 

  • Humbert PO, Grzeschik NA, Brumby AM, Galea R, Elsum I, Richardson HE . (2008). Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module. Oncogene 27: 6888–6907.

    Article  CAS  PubMed  Google Scholar 

  • Hurd TW, Gao L, Roh MH, Macara IG, Margolis B . (2003). Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nat Cell Biol 5: 137–142.

    Article  CAS  PubMed  Google Scholar 

  • Itoh M, Sasaki H, Furuse M, Ozak H, Kita T, Tsukita S . (2001). JAM binds to PAR-3: a possible mechanism behind the recruitment of PAR-3 to tight junctions. J Cell Biol 154: 491–498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Izumi Y, Hirose T, Tamai Y, Hirai S, Nagashima Y, Fujimoto T et al. (1998). An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J Cell Biol 143: 95–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeanes A, Gottardi CJ, Yap AS . (2008). Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27: 6920–6929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joberty G, Petersen C, Gao L, Macara IG . (2000). The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. Nat Cell Biol 2: 531–539.

    Article  CAS  PubMed  Google Scholar 

  • Johansson A-S, Driessens M, Aspenström P . (2000). The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. J Cell Sci 113: 3267–3275.

    Article  CAS  PubMed  Google Scholar 

  • Kaelin WG . (2005). The von Hippel–Lindau tumor suppressor protein: roles in cancer and oxygen sensing. Cold Spring Harb Symp Quant Biol 70: 159–166.

    Article  CAS  PubMed  Google Scholar 

  • Katajisto P, Vallenius T, Vaahtomeri K, Ekman N, Udd L, Tiainen M et al. (2007). The LKB1 tumor suppressor kinase in human disease. Biochim Biophys Acta 1775: 63–75.

    CAS  PubMed  Google Scholar 

  • Kemphues KJ, Priess JR, Morton DG, Cheng NS . (1988). Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52: 311–320.

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi A, Yamamoto H . (2008). Tumor formation due to abnormalities in the beta-catenin-independent pathway of Wnt signaling. Cancer Sci 99: 202–208.

    Article  CAS  PubMed  Google Scholar 

  • Knust E, Tepass U, Wodarz A . (1993). Crumbs and stardust two genes of Drosophila required for the development of epithelial cell polarity. Dev Suppl 1993: 261–268.

    Google Scholar 

  • Kolsch V, Charest PG, Firtel RA . (2008). The regulation of cell motility and chemotaxis by phospholipid signaling. J Cell Sci 121: 551–559.

    Article  CAS  PubMed  Google Scholar 

  • Kopfstein L, Christofori G . (2006). Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cell Mol Life Sci 63: 449–468.

    Article  CAS  PubMed  Google Scholar 

  • Koster MI, Roop DR . (2007). Mechanisms regulating epithelial stratification. Annu Rev Cell Dev Biol 23: 93–113.

    Article  CAS  PubMed  Google Scholar 

  • Kuphal S, Wallner S, Schimanski CC, Bataille F, Hofer P, Strand S et al. (2006). Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25: 103–110.

    Article  CAS  PubMed  Google Scholar 

  • Kuribayashi K, Nakamura K, Tanaka M, Sato T, Kato J, Sasaki K et al. (2007). Essential role of protein kinase C zeta in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP. J Cell Biol 176: 1049–1060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee M, Vasioukhin V . (2008). Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor. J Cell Sci 121: 1141–1150.

    Article  CAS  PubMed  Google Scholar 

  • Lemmers C, Michel D, Lane-Guermonprez L, Delgrossi MH, Medina E, Arsanto JP et al. (2004). CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. Mol Biol Cell 15: 1324–1333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levy L, Hill CS . (2006). Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev 17: 41–58.

    Article  CAS  PubMed  Google Scholar 

  • Lin D, Edwards AS, Fawcett JP, Mbamalu G, Scott JD, Pawson T . (2000). A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nat Cell Biol 2: 540–547.

    Article  CAS  PubMed  Google Scholar 

  • Logan CY, Nusse R . (2004). The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20: 781–810.

    Article  CAS  PubMed  Google Scholar 

  • Malliri A, van der Kammen RA, Clark K, van der Valk M, Michiels F, Collard JG . (2002). Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 417: 867–871.

    Article  CAS  PubMed  Google Scholar 

  • Manfruelli P, Arquier N, Hanratty WP, Semeriva M . (1996). The tumor suppressor gene, lethal(2)giant larvae (1(2)g1), is required for cell shape change of epithelial cells during Drosophila development. Development 122: 2283–2294.

    Article  CAS  PubMed  Google Scholar 

  • Martin-Belmonte F, Gassama A, Datta A, Yu W, Rescher U, Gerke V et al. (2007). PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42. Cell 128: 383–397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehenni H, Lin-Marq N, Buchet-Poyau K, Reymond A, Collard MA, Picard D et al. (2005). LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. Hum Mol Genet 14: 2209–2219.

    Article  CAS  PubMed  Google Scholar 

  • Merlot S, Firtel RA . (2003). Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J Cell Sci 116: 3471–3478.

    Article  CAS  PubMed  Google Scholar 

  • Mertens AE, Pegtel DM, Collard JG . (2006). Tiam1 takes PARt in cell polarity. Trends Cell Biol 16: 308–316.

    Article  CAS  PubMed  Google Scholar 

  • Murdoch JN, Henderson DJ, Doudney K, Gaston-Massuet C, Phillips HM, Paternotte C et al. (2003). Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Hum Mol Genet 12: 87–98.

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa S, Yano T, Nakagawa K, Takizawa S, Suzuki Y, Yasugi T et al. (2004). Analysis of the expression and localisation of a LAP protein, human scribble, in the normal and neoplastic epithelium of uterine cervix. Br J Cancer 90: 194–199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishimura T, Kato K, Yamaguchi T, Fukata Y, Ohno S, Kaibuchi K . (2004). Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6: 328–334.

    Article  CAS  PubMed  Google Scholar 

  • Okuda H, Saitoh K, Hirai S, Iwai K, Takaki Y, Baba M et al. (2001). The von Hippel–Lindau tumor suppressor protein mediates ubiquitination of activated atypical protein kinase C. J Biol Chem 276: 43611–43617.

    Article  CAS  PubMed  Google Scholar 

  • Osmani N, Vitale N, Borg JP, Etienne-Manneville S . (2006). Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Curr Biol 16: 2395–2405.

    Article  CAS  PubMed  Google Scholar 

  • Ossipova O, Bardeesy N, DePinho RA, Green JB . (2003). LKB1 (XEEK1) regulates Wnt signalling in vertebrate development. Nat Cell Biol 5: 889–894.

    Article  CAS  PubMed  Google Scholar 

  • Ossipova O, Dhawan S, Sokol S, Green JB . (2005). Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development. Dev Cell 8: 829–841.

    Article  CAS  PubMed  Google Scholar 

  • Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL . (2005). Regulation of the polarity protein Par6 by TGF beta receptors controls epithelial cell plasticity. Science 307: 1603–1609.

    Article  CAS  PubMed  Google Scholar 

  • Pagliarini RA, Xu T . (2003). A genetic screen in Drosophila for metastatic behavior. Science 302: 1227–1231.

    Article  CAS  PubMed  Google Scholar 

  • Pegtel DM, Ellenbroek SI, Mertens AE, van der Kammen RA, de Rooij J, Collard JG . (2007). The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity. Curr Biol 17: 1623–1634.

    Article  CAS  PubMed  Google Scholar 

  • Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G . (1998). A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392: 190–193.

    Article  CAS  PubMed  Google Scholar 

  • Pinheiro EM, Montell DJ . (2004). Requirement for Par-6 and Bazooka in Drosophila border cell migration. Development 131: 5243–5251.

    Article  CAS  PubMed  Google Scholar 

  • Plant PJ, Fawcett JP, Lin DC, Holdorf AD, Binns K, Kulkarni S et al. (2003). A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl. Nat Cell Biol 5: 301–308.

    Article  CAS  PubMed  Google Scholar 

  • Potten CS, Booth C, Pritchard DM . (1997). The intestinal epithelial stem cell: the mucosal governor. Int J Exp Pathol 78: 219–243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin Y, Capaldo C, Gumbiner BM, Macara IG . (2005). The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J Cell Biol 171: 1061–1071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Regala RP, Weems C, Jamieson L, Khoor A, Edell ES, Lohse CM et al. (2005). Atypical protein kinase C iota is an oncogene in human non-small cell lung cancer. Cancer Res 65: 8905–8911.

    Article  CAS  PubMed  Google Scholar 

  • Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G et al. (2003). Cell migration: integrating signals from front to back. Science 302: 1704–1709.

    Article  CAS  PubMed  Google Scholar 

  • Sahai E . (2005). Mechanisms of cancer cell invasion. Curr Opin Genet Dev 15: 87–96.

    Article  CAS  PubMed  Google Scholar 

  • Sander EE, van Delft S, ten Klooster JP, Reid T, van der Kammen RA, Michiels F et al. (1998). Matrix-dependent Tiam/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol 143: 1385–1398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schermer B, Ghenoiu C, Bartram M, Muller RU, Kotsis F, Hohne M et al. (2006). The von Hippel–Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth. J Cell Biol 175: 547–554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schimanski CC, Schmitz G, Kashyap A, Bosserhoff AK, Bataille F, Schafer SC et al. (2005). Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer. Oncogene 24: 3100–3109.

    Article  CAS  PubMed  Google Scholar 

  • Schlessinger K, McManus EJ, Hall A . (2007). Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity. J Cell Biol 178: 355–361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segditsas S, Tomlinson I . (2006). Colorectal cancer and genetic alterations in the Wnt pathway. Oncogene 25: 7531–7537.

    Article  CAS  PubMed  Google Scholar 

  • Shelly M, Cancedda L, Heilshorn S, Sumbre G, Poo MM . (2007). LKB1/STRAD promotes axon initiation during neuronal polarization. Cell 129: 565–577.

    Article  CAS  PubMed  Google Scholar 

  • Shi S-H, Jan LY, Jan Y-N . (2003). Hippocampal neuronal polarity specified by spacially localized mPar3/mPar6 and PI3-Kinase activity. Cell 112: 63–75.

    Article  CAS  PubMed  Google Scholar 

  • Shi SH, Cheng T, Jan LY, Jan YN . (2004). APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity. Curr Biol 14: 2025–2032.

    Article  CAS  PubMed  Google Scholar 

  • Shin K, Wang Q, Margolis B . (2007). PATJ regulates directional migration of mammalian epithelial cells. EMBO Rep 8: 158–164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siegrist SE, Doe CQ . (2007). Microtubule-induced cortical cell polarity. Genes Dev 21: 483–496.

    Article  CAS  PubMed  Google Scholar 

  • Stern CD . (2006). Evolution of the mechanisms that establish the embryonic axes. Curr Opin Genet Dev 16: 413–418.

    Article  CAS  PubMed  Google Scholar 

  • Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ et al. (2001). PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling. Nat Cell Biol 3: 628–636.

    Article  CAS  PubMed  Google Scholar 

  • Sun R, Gao P, Chen L, Ma D, Wang J, Oppenheim JJ et al. (2005). Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human breast cancer cells. Cancer Res 65: 1433–1441.

    Article  CAS  PubMed  Google Scholar 

  • Tanentzapf G, Tepass U . (2003). Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol 5: 46–52.

    Article  CAS  PubMed  Google Scholar 

  • Tapon N . (2003). Modeling transformation and metastasis in Drosophila. Cancer Cell 4: 333–335.

    Article  CAS  PubMed  Google Scholar 

  • Tepass U, Theres C, Knust E . (1990). Crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia. Cell 61: 787–799.

    Article  CAS  PubMed  Google Scholar 

  • Thiery JP, Huang R . (2005). Linking epithelial-mesenchymal transition to the well-known polarity protein Par6. Dev Cell 8: 456–458.

    Article  CAS  PubMed  Google Scholar 

  • Thomas M, Massimi P, Navarro C, Borg JP, Banks L . (2005). The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins. Oncogene 24: 6222–6230.

    Article  CAS  PubMed  Google Scholar 

  • Thomas M, Narayan N, Pim D, Tomaic V, Massimi P, Nagasaka K et al. (2008). Human papillomaviruses, cervical cancer and cell polarity. Oncogene 27: 7018–7030.

    Article  CAS  PubMed  Google Scholar 

  • von Stein W, Ramrath A, Grimm A, Muller-Borg M, Wodarz A . (2005). Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development 132: 1675–1686.

    Article  CAS  PubMed  Google Scholar 

  • Wada H, Iwasaki M, Sato T, Masai I, Nishiwaki Y, Tanaka H et al. (2005). Dual roles of zygotic and maternal Scribble1 in neural migration and convergent extension movements in zebrafish embryos. Development 132: 2273–2285.

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Margolis B . (2007). Apical junctional complexes and cell polarity. Kidney Int 72: 1448–1458.

    Article  CAS  PubMed  Google Scholar 

  • Wang HR, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH et al. (2003). Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science 302: 1775–1779.

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Hurd TW, Margolis B . (2004). Tight junction protein Par6 interacts with an evolutionarily conserved region in the amino terminus of PALS1/stardust. J Biol Chem 279: 30715–30721.

    Article  CAS  PubMed  Google Scholar 

  • Wodarz A, Nathke I . (2007). Cell polarity in development and cancer. Nat Cell Biol 9: 1016–1024.

    Article  CAS  PubMed  Google Scholar 

  • Woodhouse E, Hesperger E, Shearn A . (1998). Growth, metastasis and invasiveness of Drosophila tumors caused by mutations in specific tumor suppressor genes. Dev Genes Evol 207: 542–550.

    Article  CAS  PubMed  Google Scholar 

  • Yamada T, Horikoshi Y, Sygiyama Y, Ishiyama C, Suzuki A, Hirose T et al. (2003). Mammalian Lgl forms a proteins complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr Biol 13: 734–743.

    Article  Google Scholar 

  • Yamanaka T, Horikoshi Y, Izumi N, Suzuki A, Mizuno K, Ohno S . (2006). Lgl mediates apical domain disassembly by suppressing the PAR-3-aPKC-PAR-6 complex to orient apical membrane polarity. J Cell Sci 119: 2107–2118.

    Article  CAS  PubMed  Google Scholar 

  • Zarbalis K, May SR, Shen Y, Ekker M, Rubenstein JL, Peterson AS . (2004). A focused and efficient genetic screening strategy in the mouse: identification of mutations that disrupt cortical development. PLoS Biol 2: E219.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang L, Huang J, Yang N, Liang S, Barchetti A, Giannakakis A et al. (2006). Integrative genomic analysis of protein kinase C (PKC) family identifies PKCiota as a biomarker and potential oncogene in ovarian carcinoma. Cancer Res 66: 4627–4635.

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Schafer-Hales K, Khuri FR, Zhou W, Vertino PM, Marcus AI . (2008). The tumor suppressor LKB1 regulates lung cancer cell polarity by mediating cdc42 recruitment and activity. Cancer Res 68: 740–748.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Zhu J, Yang GY, Wang QJ, Qian L, Chen YM et al. (2007). Dishevelled promotes axon differentiation by regulating atypical protein kinase C. Nat Cell Biol 9: 743–754.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We apologize for those authors whose work was not cited directly owing to space limitation. This work was supported by grants from the l'Agence Nationale pour la Recherche, la Fondation de France, La Ligue contre le Cancer et l'Association pour la Recherche sur le Cancer, la Fondation Schlumberger pour l'Enseignement et la Recherche, the EMBO Young Investigator Program.

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  1. Cell polarity and migration group, Institut Pasteur and CNRS URA 2582, Paris cedex 15, France

    S Etienne-Manneville

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Correspondence to S Etienne-Manneville.

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Etienne-Manneville, S. Polarity proteins in migration and invasion. Oncogene 27, 6970–6980 (2008). https://doi.org/10.1038/onc.2008.347

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