Abstract
There are now clear indications that endocytosis and recycling of integrins is important during cancer progression, invasion and metastasis. In this chapter, we will review the recent literature outlining the cellular mechanisms that control integrin endocytosis, endocytic trafficking and recycling and how these processes may be measured experimentally. The influence of endocytic processes on integrin function will then be considered, such as how the spatial dynamics of integrins are controlled in migrating cells. We will then focus on the various ways that integrin trafficking can influence cancer cell migration and invasion. In particular, we will highlight (a) how α5β1 integrin and receptor tyrosine kinase (RTK) recycling is upregulated following αvβ3 inhibition as this provides a molecular explanation for the overall lack of efficacy of anti-αv integrin drugs in tumour angiogenesis; (b) how trafficking events can dictate whether certain GTPases, such as Rab25, function as tumour suppressors or promoters; and (c) how mutation of p53 drives invasion and metastasis by altering integrin and RTK recycling, and we will discuss whether components of these membrane trafficking pathways may be targeted therapeutically to reverse oncogenic drive in human cancers.
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Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687
Sahai E (2005) Mechanisms of cancer cell invasion. Curr Opin Genet Dev 15(1):87–96
Sahai E, Marshall CJ (2002) RHO-GTPases and cancer. Nat Rev Cancer 2(2):133–142
Grant BD, Donaldson JG (2009) Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 10(9):597–608
Bretscher MS (1989) Endocytosis and recycling of the fibronectin receptor in CHO cells. EMBO J 8(5):1341–1348
Bretscher MS (1992) Circulating integrins: alpha 5 beta 1, alpha 6 beta 4 and Mac-1, but not alpha 3 beta 1, alpha 4 beta 1 or LFA-1. EMBO J 11(2):405–410
Caswell PT, Norman JC (2006) Integrin trafficking and the control of cell migration. Traffic 7(1):14–21
Pellinen T, Ivaska J (2006) Integrin traffic. J Cell Sci 119(pt 18):3723–3731
Altankov G, Grinnell F (1995) Fibronectin receptor internalization and AP-2 complex reorganization in potassium-depleted fibroblasts. Exp Cell Res 216(2):299–309
Bretscher MS (1996) Moving membrane up to the front of migrating cells. Cell 85(4):465–467
Dozynkiewicz MA, Jamieson NB, Macpherson I, Grindlay J, van den Berghe PV, von Thun A et al (2012) Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell 22(1):131–145
Caswell PT, Spence HJ, Parsons M, White DP, Clark K, Cheng KW et al (2007) Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell 13(4):496–510
Caswell PT, Chan M, Lindsay AJ, McCaffrey MW, Boettiger D, Norman JC (2008) Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J Cell Biol 183(1):143–155
Roberts M, Barry S, Woods A, van der Sluijs P, Norman J (2001) PDGF-regulated rab4-dependent recycling of alphavbeta3 integrin from early endosomes is necessary for cell adhesion and spreading. Curr Biol 11(18):1392–1402
Pellinen T, Arjonen A, Vuoriluoto K, Kallio K, Fransen JA, Ivaska J (2006) Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of {beta}1-integrins. J Cell Biol 173(5):767–780
Powelka AM, Sun J, Li J, Gao M, Shaw LM, Sonnenberg A et al (2004) Stimulation-dependent recycling of integrin beta1 regulated by ARF6 and Rab11. Traffic 5(1):20–36
Arjonen A, Alanko J, Veltel S, Ivaska J (2012) Distinct recycling of active and inactive beta1 integrins. Traffic. 13(4):610–625
Chao WT, Kunz J (2009) Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins. FEBS Lett 583(8):1337–1343
Valdembri D, Caswell PT, Anderson KI, Schwarz JP, Konig I, Astanina E et al (2009) Neuropilin-1/GIPC1 signaling regulates alpha5beta1 integrin traffic and function in endothelial cells. PLoS Biol 7(1):e25
Reid PA, Watts C (1990) Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments. Nature 346(6285):655–657
Strous GJ, Du Maine A, Zijderhand-Bleekemolen JE, Slot JW, Schwartz AL (1985) Effect of lysosomotropic amines on the secretory pathway and on the recycling of the asialoglycoprotein receptor in human hepatoma cells. J Cell Biol 101(2):531–539
Ezratty EJ, Bertaux C, Marcantonio EE, Gundersen GG (2009) Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells. J Cell Biol 187(5):733–747
Lippincott-Schwartz J, Patterson GH (2008) Fluorescent proteins for photoactivation experiments. Methods Cell Biol 85:45–61
Jovic M, Naslavsky N, Rapaport D, Horowitz M, Caplan S (2007) EHD1 regulates beta1 integrin endosomal transport: effects on focal adhesions, cell spreading and migration. J Cell Sci 120(pt 5):802–814
Roberts MS, Woods AJ, Dale TC, Van Der Sluijs P, Norman JC (2004) Protein kinase B/Akt acts via glycogen synthase kinase 3 to regulate recycling of alpha v beta 3 and alpha 5 beta 1 integrins. Mol Cell Biol 24(4):1505–1515
Serrels A, Timpson P, Canel M, Schwarz JP, Carragher NO, Frame MC et al (2009) Real-time study of E-cadherin and membrane dynamics in living animals: implications for disease modeling and drug development. Cancer Res 69(7):2714–2719
Teckchandani A, Toida N, Goodchild J, Henderson C, Watts J, Wollscheid B et al (2009) Quantitative proteomics identifies a Dab2/integrin module regulating cell migration. J Cell Biol 186(1):99–111
Howes MT, Kirkham M, Riches J, Cortese K, Walser PJ, Simpson F et al (2010) Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. J Cell Biol 190(4):675–691
Shi F, Sottile J (2008) Caveolin-1-dependent beta1 integrin endocytosis is a critical regulator of fibronectin turnover. J Cell Sci 121(pt 14):2360–2371
Gu Z, Noss EH, Hsu VW, Brenner MB (2011) Integrins traffic rapidly via circular dorsal ruffles and macropinocytosis during stimulated cell migration. J Cell Biol 193(1):61–70
Ezratty EJ, Partridge MA, Gundersen GG (2005) Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7(6):581–590
Teckchandani A, Mulkearns EE, Randolph TW, Toida N, Cooper JA (2012) The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis. Mol Cell Biol 23(15):2905–2916
Nishimura T, Kaibuchi K (2007) Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3. Dev Cell 13(1):15–28
Dunphy JL, Moravec R, Ly K, Lasell TK, Melancon P, Casanova JE (2006) The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins. Curr Biol 16(3):315–320
Moravec R, Conger KK, D’Souza R, Allison AB, Casanova JE (2012) BRAG2/GEP100/IQSec1 interacts with clathrin and regulates alpha5beta1 integrin endocytosis through activation of Arf5. J Biol Chem 287(37):31138–31147
Chen WJ, Goldstein JL, Brown MS (1990) NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. J Biol Chem 265(6):3116–3123
Rajagopalan M, Neidigh JL, McClain DA (1991) Amino acid sequences Gly-Pro-Leu-Tyr and Asn-Pro-Glu-Tyr in the submembranous domain of the insulin receptor are required for normal endocytosis. J Biol Chem 266(34):23068–23073
Vignoud L, Usson Y, Balzac F, Tarone G, Block MR (1994) Internalization of the alpha 5 beta 1 integrin does not depend on “NPXY” signals. Biochem Biophys Res Commun 199(2):603–611
Margadant C, Kreft M, de Groot DJ, Norman JC, Sonnenberg A (2012) Distinct roles of Talin and Kindlin in regulating integrin alpha5beta1 function and trafficking. Curr Biol 22(17):1554–1563
Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H et al (2008) Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell 15(3):371–385
Calderwood DA, Fujioka Y, de Pereda JM, Garcia-Alvarez B, Nakamoto T, Margolis B et al (2003) Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling. Proc Natl Acad Sci U S A 100(5):2272–2277
Garcia-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID et al (2003) Structural determinants of integrin recognition by talin. Mol Cell 11(1):49–58
McCleverty CJ, Lin DC, Liddington RC (2007) Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions. Protein Sci 16(6):1223–1229
Mai A, Veltel S, Pellinen T, Padzik A, Coffey E, Marjomaki V et al (2011) Competitive binding of Rab21 and p120RasGAP to integrins regulates receptor traffic and migration. J Cell Biol 194(2):291–306
Ramsay AG, Keppler MD, Jazayeri M, Thomas GJ, Parsons M, Violette S et al (2007) HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin alphavbeta6. Cancer Res 67(11):5275–5284
Fabbri M, Di Meglio S, Gagliani MC, Consonni E, Molteni R, Bender JR et al (2005) Dynamic partitioning into lipid rafts controls the endo-exocytic cycle of the alphaL/beta2 integrin, LFA-1, during leukocyte chemotaxis. Mol Biol Cell 16(12):5793–5803
Galvez BG, Matias-Roman S, Yanez-Mo M, Vicente-Manzanares M, Sanchez-Madrid F, Arroyo AG (2004) Caveolae are a novel pathway for membrane-type 1 matrix metalloproteinase traffic in human endothelial cells. Mol Biol Cell 15(2):678–687
Wickstrom SA, Lange A, Hess MW, Polleux J, Spatz JP, Kruger M et al (2010) Integrin-linked kinase controls microtubule dynamics required for plasma membrane targeting of caveolae. Dev Cell 19(4):574–588
Bass MD, Williamson RC, Nunan RD, Humphries JD, Byron A, Morgan MR et al (2011) A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Dev Cell 21(4):681–693
Hansen CG, Nichols BJ (2009) Molecular mechanisms of clathrin-independent endocytosis. J Cell Sci 122(pt 11):1713–1721
Lundmark R, Doherty GJ, Howes MT, Cortese K, Vallis Y, Parton RG et al (2008) The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway. Curr Biol 18(22):1802–1808
Doherty GJ, Ahlund MK, Howes MT, Moren B, Parton RG, McMahon HT et al (2011) The endocytic protein GRAF1 is directed to cell-matrix adhesion sites and regulates cell spreading. Mol Biol Cell 22(22):4380–4389
Orth JD, McNiven MA (2006) Get off my back! Rapid receptor internalization through circular dorsal ruffles. Cancer Res 66(23):11094–11096
Orth JD, Krueger EW, Weller SG, McNiven MA (2006) A novel endocytic mechanism of epidermal growth factor receptor sequestration and internalization. Cancer Res 66(7):3603–3610
Bar-Sagi D, Hall A (2000) Ras and Rho GTPases: a family reunion. Cell 103(2):227–238
Parsons M, Keppler MD, Kline A, Messent A, Humphries MJ, Gilchrist R et al (2002) Site-directed perturbation of protein kinase C-integrin interaction blocks carcinoma cell chemotaxis. Mol Cell Biol 22(16):5897–5911
Ng T, Shima D, Squire A, Bastiaens PI, Gschmeissner S, Humphries MJ et al (1999) PKCalpha regulates beta1 integrin-dependent cell motility through association and control of integrin traffic. EMBO J 18(14):3909–3923
Upla P, Marjomaki V, Kankaanpaa P, Ivaska J, Hyypia T, Van Der Goot FG et al (2004) Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization. Mol Biol Cell 15(2):625–636
Couchman JR, Woods A (1999) Syndecan-4 and integrins: combinatorial signaling in cell adhesion. J Cell Sci 112(pt 20):3415–3420
Hines JH, Abu-Rub M, Henley JR (2010) Asymmetric endocytosis and remodeling of beta1-integrin adhesions during growth cone chemorepulsion by MAG. Nat Neurosci 13(7):829–837
Du J, Chen X, Liang X, Zhang G, Xu J, He L et al (2011) Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity. Proc Natl Acad Sci U S A 108(23):9466–9471
Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT et al (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139(5):891–906
Naslavsky N, Weigert R, Donaldson JG (2003) Convergence of non-clathrin- and clathrin-derived endosomes involves Arf6 inactivation and changes in phosphoinositides. Mol Biol Cell 14(2):417–431
Woods AJ, White DP, Caswell PT, Norman JC (2004) PKD1/PKCmu promotes alphavbeta3 integrin recycling and delivery to nascent focal adhesions. EMBO J 23(13):2531–2543
White DP, Caswell PT, Norman JC (2007) alpha v beta3 and alpha5beta1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration. J Cell Biol 177(3):515–525
di Blasio L, Droetto S, Norman J, Bussolino F, Primo L (2010) Protein kinase D1 regulates VEGF-A-induced alphavbeta3 integrin trafficking and endothelial cell migration. Traffic 11(8):1107–1118
Ochi N, Tanasanvimon S, Matsuo Y, Tong Z, Sung B, Aggarwal BB et al (2011) Protein kinase D1 promotes anchorage-independent growth, invasion, and angiogenesis by human pancreatic cancer cells. J Cell Physiol 226(4):1074–1081
Eiseler T, Doppler H, Yan IK, Goodison S, Storz P (2009) Protein kinase D1 regulates matrix metalloproteinase expression and inhibits breast cancer cell invasion. Breast Cancer Res 11(1):R13
Kim M, Jang HR, Kim JH, Noh SM, Song KS, Cho JS et al (2008) Epigenetic inactivation of protein kinase D1 in gastric cancer and its role in gastric cancer cell migration and invasion. Carcinogenesis 29(3):629–637
Zhang K, Ye C, Zhou Q, Zheng R, Lv X, Chen Y et al (2007) PKD1 inhibits cancer cells migration and invasion via Wnt signaling pathway in vitro. Cell Biochem Funct 25(6):767–774
Fang Z, Takizawa N, Wilson KA, Smith TC, Delprato A, Davidson MW et al (2010) The membrane-associated protein, supervillin, accelerates F-actin-dependent rapid integrin recycling and cell motility. Traffic 11(6):782–799
Skalski M, Coppolino MG (2005) SNARE-mediated trafficking of alpha5beta1 integrin is required for spreading in CHO cells. Biochem Biophys Res Commun 335(4):1199–1210
Strachan LR, Condic ML (2004) Cranial neural crest recycle surface integrins in a substratum-dependent manner to promote rapid motility. J Cell Biol 167(3):545–554
Yoon SO, Shin S, Mercurio AM (2005) Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin. Cancer Res 65(7):2761–2769
Jovic M, Kieken F, Naslavsky N, Sorgen PL, Caplan S (2009) Eps15 homology domain 1-associated tubules contain phosphatidylinositol-4-phosphate and phosphatidylinositol-(4,5)-bisphosphate and are required for efficient recycling. Mol Biol Cell 20(11):2731–2743
Naslavsky N, Caplan S (2011) EHD proteins: key conductors of endocytic transport. Trends Cell Biol 21(2):122–131
Sharma M, Giridharan SS, Rahajeng J, Naslavsky N, Caplan S (2009) MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling. Mol Biol Cell 20(24):5181–5194
Day P, Riggs KA, Hasan N, Corbin D, Humphrey D, Hu C (2011) Syntaxins 3 and 4 mediate vesicular trafficking of alpha5beta1 and alpha3beta1 integrins and cancer cell migration. Int J Oncol 39(4):863–871
Hasan N, Hu C (2010) Vesicle-associated membrane protein 2 mediates trafficking of alpha5beta1 integrin to the plasma membrane. Exp Cell Res 316(1):12–23
Luftman K, Hasan N, Day P, Hardee D, Hu C (2009) Silencing of VAMP3 inhibits cell migration and integrin-mediated adhesion. Biochem Biophys Res Commun 380(1):65–70
Rapaport D, Lugassy Y, Sprecher E, Horowitz M (2010) Loss of SNAP29 impairs endocytic recycling and cell motility. PLoS One 5(3):e9759
Veale KJ, Offenhauser C, Whittaker SP, Estrella RP, Murray RZ (2010) Recycling endosome membrane incorporation into the leading edge regulates lamellipodia formation and macrophage migration. Traffic 11(10):1370–1379
Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE et al (1999) Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Mol Biol Cell 10(1):47–61
Cohen P, Frame S (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2(10):769–776
Dai J, Li J, Bos E, Porcionatto M, Premont RT, Bourgoin S et al (2004) ACAP1 promotes endocytic recycling by recognizing recycling sorting signals. Dev Cell 7(5):771–776
Li J, Ballif BA, Powelka AM, Dai J, Gygi SP, Hsu VW (2005) Phosphorylation of ACAP1 by Akt regulates the stimulation-dependent recycling of integrin beta1 to control cell migration. Dev Cell 9(5):663–673
Ivaska J, Whelan RD, Watson R, Parker PJ (2002) PKC epsilon controls the traffic of beta1 integrins in motile cells. EMBO J 21(14):3608–3619
Ivaska J, Vuoriluoto K, Huovinen T, Izawa I, Inagaki M, Parker PJ (2005) PKCepsilon-mediated phosphorylation of vimentin controls integrin recycling and motility. EMBO J 24(22):3834–3845
Chan PC, Chen HC (2012) p120RasGAP-mediated activation of c-Src is critical for oncogenic Ras to induce tumor invasion. Cancer Res 72(9):2405–2415
Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S et al (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139(7):1327–1341
Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, van den Berghe PV et al (2012) Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene. Epub 2012/05/15.
Lindsay AJ, McCaffrey MW (2004) The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane. J Cell Sci 117(pt 19):4365–4375
Jenkins GM, Frohman MA (2005) Phospholipase D: a lipid centric review. Cell Mol Life Sci 62(19–20):2305–2316
Merida I, Avila-Flores A, Merino E (2008) Diacylglycerol kinases: at the hub of cell signalling. Biochem J 409(1):1–18
Rainero E, Caswell PT, Muller PA, Grindlay J, McCaffrey MW, Zhang Q et al (2012) Diacylglycerol kinase alpha controls RCP-dependent integrin trafficking to promote invasive migration. J Cell Biol 196(2):277–295
Brown FC, Pfeffer SR (2010) An update on transport vesicle tethering. Mol Membr Biol 27(8):457–461
Lobert VH, Brech A, Pedersen NM, Wesche J, Oppelt A, Malerod L et al (2010) Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes. Dev Cell 19(1):148–159
Nam KT, Lee HJ, Smith JJ, Lapierre LA, Kamath VP, Chen X et al (2010) Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. J Clin Invest 120(3):840–849
Cheng JM, Volk L, Janaki DK, Vyakaranam S, Ran S, Rao KA (2010) Tumor suppressor function of Rab25 in triple-negative breast cancer. Int J Cancer 126(12):2799–2812
Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N et al (2004) The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 10(11):1251–1256
Agarwal R, Jurisica I, Mills GB, Cheng KW (2009) The emerging role of the RAB25 small GTPase in cancer. Traffic 10(11):1561–1568
Sadok A, Pierres A, Dahan L, Prevot C, Lehmann M, Kovacic H (2009) NADPH oxidase 1 controls the persistence of directed cell migration by a Rho-dependent switch of alpha2/alpha3 integrins. Mol Cell Biol 29(14):3915–3928
Chao WT, Ashcroft F, Daquinag AC, Vadakkan T, Wei Z, Zhang P et al (2010) Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting beta1 integrin endocytosis. Mol Cell Biol 30(18):4463–4479
Jekely G, Sung HH, Luque CM, Rorth P (2005) Regulators of endocytosis maintain loc.lized receptor tyrosine kinase signaling in guided migration. Dev Cell 9(2):197–207
Palamidessi A, Frittoli E, Garre M, Faretta M, Mione M, Testa I et al (2008) Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134(1):135–147
Rappoport JZ, Simon SM (2003) Real-time analysis of clathrin-mediated endocytosis during cell migration. J Cell Sci 116(pt 5):847–855
Laukaitis CM, Webb DJ, Donais K, Horwitz AF (2001) Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells. J Cell Biol 153(7):1427–1440
Hopkins CR, Gibson A, Shipman M, Strickland DK, Trowbridge IS (1994) In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella. J Cell Biol 125(6):1265–1274
Prigozhina NL, Waterman-Storer CM (2004) Protein kinase D-mediated anterograde membrane trafficking is required for fibroblast motility. Curr Biol 14(2):88–98
Schmoranzer J, Kreitzer G, Simon SM (2003) Migrating fibroblasts perform polarized, microtubule-dependent exocytosis towards the leading edge. J Cell Sci 116(pt 22):4513–4519
Singh RK, Liao W, Tracey-White D, Recchi C, Tolmachova T, Rankin SM et al (2012) Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment. J Cell Sci 125(pt 7):1652–1656
Hognas G, Tuomi S, Veltel S, Mattila E, Murumagi A, Edgren H et al (2012) Cytokinesis failure due to derailed integrin traffic induces aneuploidy and oncogenic transformation in vitro and in vivo. Oncogene 31(31):3597–3606
Danen EH, van Rheenen J, Franken W, Huveneers S, Sonneveld P, Jalink K et al (2005) Integrins control motile strategy through a Rho-cofilin pathway. J Cell Biol 169(3):515–526
Sturge J, Wienke D, Isacke CM (2006) Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180 to promote adhesion disassembly. J Cell Biol 175(2):337–347
Nisato RE, Tille JC, Jonczyk A, Goodman SL, Pepper MS (2003) alphav beta 3 and alphav beta 5 integrin antagonists inhibit angiogenesis in vitro. Angiogenesis 6(2):105–119
Stupp R, Ruegg C (2007) Integrin inhibitors reaching the clinic. J Clin Oncol 25(13):1637–1638
Tucker GC (2006) Integrins: molecular targets in cancer therapy. Curr Oncol Rep 8(2):96–103
Reynolds AR, Hart IR, Watson AR, Welti JC, Silva RG, Robinson SD et al (2009) Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med 15(4):392–400
Weller M, Reardon D, Nabors B, Stupp R (2009) Will integrin inhibitors have proangiogenic effects in the clinic? Nat Med 15(7):726; author reply 7
Dechantsreiter MA, Planker E, Matha B, Lohof E, Holzemann G, Jonczyk A et al (1999) N-methylated cyclic RGD peptides as highly active and selective alpha(V)beta(3) integrin antagonists. J Med Chem 42(16):3033–3040
Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X et al (2002) Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 8(1):27–34
Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N et al (2005) Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J Cell Biol 171(6):1023–1034
Oren M, Rotter V (2010) Mutant p53 gain-of-function in cancer. Cold Spring Harb Perspect Biol 2(2):a001107
Adorno M, Cordenonsi M, Montagner M, Dupont S, Wong C, Hann B et al (2009) A mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 137(1):87–98
Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D et al (2005) Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7(4):363–373
Guo X, Keyes WM, Papazoglu C, Zuber J, Li W, Lowe SW et al (2009) TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol 11(12):1451–1457
Acknowledgements
Work in the Norman lab is funded by Cancer Research UK. Elena Rainero is supported by a fellowship from the West of Scotland Women’s Bowling Association.
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Rainero, E., van den Berghe, P.V.E., Norman, J.C. (2013). Internalisation, Endosomal Trafficking and Recycling of Integrins During Cell Migration and Cancer Invasion. In: Yarden, Y., Tarcic, G. (eds) Vesicle Trafficking in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6528-7_16
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