Abstract
The epidermal growth factor receptor (EGFR) regulates a plethora of cellular and tissue functions in epithelia including cell division, survival, differentiation, and migration. EGFR signaling is up-regulated in pathologies involving aberrant growth like squamous cancer, and facilitates neoplastic progression. Many mechanisms through which the effects of EGFR are modulated in normal and pathological processes have been identified. In particular, recent research has yielded important and surprising insights into the effects of EGFR-dependent signaling on cutaneous biology and carcinogenesis. This review focuses on EGFR signaling in normal biology and squamous cancer, with emphasis on the skin as a model organ to illustrate the biological significance of EGFR signaling.
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References
Abud HE, Watson N, Heath JK (2005) Growth of intestinal epithelium in organ culture is dependent on EGF signalling. Exp Cell Res 303:252–262
Andl CD, Mizushima T, Nakagawa H, Oyama K, Harada H, Chruma K, Herlyn M, Rustgi AK (2003) Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem 278:1824–1830
Andl CD, Mizushima T, Oyama K, Bowser M, Nakagawa H, Rustgi AK (2004) EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. Am J Physiol Gastrointest Liver Physiol 287:G1227–G1237
Arcidiacono MV, Sato T, varez-Hernandez D, Yang J, Tokumoto M, Gonzalez-Suarez I, Lu Y, Tominaga Y, Cannata-Andia J, Slatopolsky Dusso AS (2008) EGFR activation increases parathyroid hyperplasia and calcitriol resistance in kidney disease. J Am Soc Nephrol 19:310–320
Bender K, Blattner C, Knebel A, Iordanov M, Herrlich P, Rahmsdorf HJ (1997) UV-induced signal transduction. J Photochem Photobiol B 37:1–17
Bhola NE, Grandis JR (2008) Crosstalk between G-protein-coupled receptors and epidermal growth factor receptor in cancer. Front Biosci 13:1857–1865
Brandt R, Eisenbrandt R, Leenders F, Zschiesche W, Binas B, Juergensen C, Theuring F (2000) Mammary gland specific hEGF receptor transgene expression induces neoplasia and inhibits differentiation. Oncogene 19:2129–2137
Canguilhem B, Pradines A, Baudouin C, Boby C, Lajoie-Mazenc I, Charveron M, Favre G (2005) RhoB protects human keratinocytes from UVB-induced apoptosis through epidermal growth factor receptor signaling. J Bio chem 280:43257–43263
Casanova ML, Larcher F, Casanova B, Murillas R, Fernandez-Acenero MJ, Villanueva C, Martinez-Palacio J, Ullrich A, Conti CJ, Jorcano JL (2002) A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis 2. Cancer Res 62:3402–3407
Chen P, Xie H, Sekar MC, Gupta K, Wells A (1994) Epidermal growth factor receptor-mediated cell motility: phospholipase C activity is required, but mitogen-activated protein kinase activity is not sufficient for induced cell movement. J Cell Biol 127:847–857
Chin YE, Kitagawa M, Kuida K, Flavell RA, Fu XY (1997) Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis. Mol Cell Biol 17:5328–5337
Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160–1174
Citri A, Yarden Y (2006) EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol 7:505–516
Coffey RJ, Derynck R, Wilcox JN, Bringman TS, Goustin AS, Moses HL, Pittelkow MR (1987) Production and auto-induction of transforming growth factor- alpha in human keratinocytes. Nature 328:817–820
Cook PW, Mattox PA, Keeble WW, Pittelkow MR, Plowman GD, Shoyab M, Adelman JP, Shipley GD (1991) A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. Mol Cell Biol 11:2547–2557
Croyle M, Akeno N, Knauf JA, Fabbro D, Chen X, Baumgartner JE, Lane HA, Fagin JA (2008) RET/PTC-induced cell growth is mediated in part by epidermal growth factor receptor (EGFR) activation: evidence for molecular and functional interactions between RET and EGFR. Cancer Res 68:4183–4191
Dassonville O, Formento JL, Francoual M, Ramaioli A, Santini J, Schneider M, Demard F, Milano G (1993) Expression of epidermal growth factor receptor and survival in upper aerodigestive tract cancer. J Clin Oncol 11:1873–1878
Dise RS, Frey MR, Whitehead RH, Polk DB (2008) Epidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 294:G276–G285
Dlugosz AA, Hansen L, Cheng C, Alexander N, Denning MF, Threadgill DW, Magnuson T, Coffey RJ Jr, Yuspa SH (1997) Targeted disruption of the epidermal growth factor receptor impairs growth of squamous papillomas expressing the v-ras Ha oncogene but does not block in vitro keratinocyte responses to oncogenic ras. Cancer Res 57:3180–3188
Donnini S, Finetti F, Solito R, Terzuoli E, Sacchetti A, Morbidelli L, Patrignani P, Ziche M (2007) EP2 prostanoid receptor promotes SCC growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways. FASEB J 21:2418–2430
Duh G, Mouri N, Warburton D, Thomas DW (2000) EGF regulates early embryonic mouse gut development in chemically defined organ culture. Pediatr Res 48:794–802
Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Aspects Med 29:258–289
El Abaseri TB, Fuhrman J, Trempus C, Shendrik I, Tennant RW, Hansen LA (2005) Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the epidermal growth factor receptor. Cancer Res 65:3958–3965
El Abaseri TB, Putta S, Hansen LA (2006) Ultraviolet irradiation induces keratinocyte proliferation and epidermal hyperplasia through the activation of the epidermal growth factor receptor. Carcinogenesis 27:225–231
Fagin JA (2004) How thyroid tumors start and why it matters: kinase mutants as targets for solid cancer pharmacotherapy. J Endocrinol 183:249–256
Falls DL (2003) Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 284:14–30
Fischer OM, Hart S, Gschwind A, Ullrich A (2003) EGFR signal transactivation in cancer cells. Biochem Soc Trans 31:1203–1208
Forsberg S, Ostman A, Rollman O (2008) Regeneration of human epidermis on acellular dermis is impeded by small-molecule inhibitors of EGF receptor tyrosine kinase. Arch Dermatol Res 300:505–516
Freeman M (2004) Proteolysis within the membrane: rhomboids revealed. Nat Rev Mol Cell Biol 5:188–197
Frusic-Zlotkin M, Raichenberg D, Wang X, David M, Michel B, Milner Y (2006) Apoptotic mechanism in pemphigus autoimmunoglobulins-induced acantholysis–possible involvement of the EGF receptor. Autoimmunity 39:563–575
Fuchs E (1990) Epidermal differentiation. Curr Opin Cell Biol 2:1028–1035
Fuchs E (2008) Skin stem cells: rising to the surface. J Cell Biol 180:273–284
Getsios S, Simpson CL, Kojima S, Harmon R, Sheu LJ, Dusek RL, Cornwell M, Green KJ (2009) Desmoglein 1-dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis. J Cell Biol 185:1243–1258
Guy PM, Platko JV, Cantley LC, Cerione RA, Carraway KL III (1994) Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase activity. Proc Natl Acad Sci USA 91:8132–8136
Hallman MA, Zhuang S, Schnellmann RG (2008) Regulation of dedifferentiation and redifferentiation in renal proximal tubular cells by the epidermal growth factor receptor. J Pharmacol Exp Ther 325:520–528
Hama T, Yuza Y, Saito Y, Uchi J, Kondo S, Okabe M, Yamada H, Kato T, Moriyama H, Kurihara S, Urashima M (2009) Prognostic significance of epidermal growth factor receptor phosphorylation and mutation in head and neck squamous cell carcinoma. Oncologist 14(9):900–908
Han CY, Lim SC, Choi HS, Kang KW (2008) Induction of ErbB2 by ultraviolet A irradiation: potential role in malignant transformation of keratinocytes. Cancer Sci 99:502–509
Hansen LA, Lichti U, Tennenbaum T, Dlugosz AA, Threadgill DW, Magnuson T, Yuspa SH (1996) Altered hair follicle morphogenesis in epidermal growth factor receptor deficient mice. In: Van Neste DJJ, Randall VA (eds) Hair research for the next millennium. Elsevier Science BV, Amsterdam, pp 425–431
Hansen LA, Alexander N, Hogan ME, Sundberg JP, Dlugosz A, Threadgill DW, Magnuson T, Yuspa SH (1997) Genetically null mice reveal a central role for epidermal growth factor receptor in the differentiation of the hair follicle and normal hair development. Am J Pathol 150:1959–1975
Hansen LA, Woodson RL II, Holbus S, Strain K, Lo Y-C, Yuspa SH (2000) The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors. Cancer Res 60:3328–3332
Hashimoto K (2000) Regulation of keratinocyte function by growth factors. J Dermatol Sci 24 (Suppl) 1:S46–S50
Hashimoto K, Higashiyama S, Asada H, Hashimura E, Kobayashi T, Sudo K, Nakagawa T, Damm D, Yoshikawa K, Taniguchi N (1994) Heparin-binding epidermal growth factor-like growth factor is an autocrine growth factor for human keratinocytes. J Biol Chem 269:20060–20066
Huang RP, Wu JX, Fan Y, Adamson ED (1996) UV activates growth factor receptors via reactive oxygen intermediates. J Cell Biol 133:211–220
Hyatt DC, Ceresa BP (2008) Cellular localization of the activated EGFR determines its effect on cell growth in MDA-MB-468 cells. Exp Cell Res 314:3415–3425
Hynes NE, Macdonald G (2009) ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol 21:177–184
Jarboe MD, Juno RJ, Stehr W, Bernal NP, Profitt S, Erwin CR, Warner BW (2005) Epidermal growth factor receptor signaling regulates goblet cell production after small bowel resection. J Pediatr Surg 40:92–97
Kashiwagi M, Kuroki T, Huh N (1997) Specific inhibition of hair follicle formation by epidermal growth factor in an organ culture of developing mouse skin. Dev Biol 189:22–32
Klapper LN, Kirschbaum MH, Sela M, Yarden Y (2000) Biochemical and clinical implications of the ErbB/HER signaling network of growth factor receptors. Adv Cancer Res 77:25–79
Knebel A, Rahmsdorf HJ, Ullrich A, Herrlich P (1996) Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents. EMBO J 15:5314–5325
Koch S, Nusrat A (2009) Dynamic regulation of epithelial cell fate and barrier function by intercellular junctions. Ann NY Acad Sci 1165:220–227
Koivisto L, Jiang G, Hakkinen L, Chan B, Larjava H (2006) HaCaT keratinocyte migration is dependent on epidermal growth factor receptor signaling and glycogen synthase kinase-3alpha. Exp Cell Res 312:2791–2805
Kolev V, Mandinova A, Guinea-Viniegra J, Hu B, Lefort K, Lambertini C, Neel V, Dummer R, Wagner EF, Dotto GP (2008) EGFR signalling as a negative regulator of Notch1 gene transcription and function in proliferating keratinocytes and cancer. Nat Cell Biol 10:902–911
Koster MI, Roop DR (2007) Mechanisms regulating epithelial stratification. Annu Rev Cell Dev Biol 23:93–113
Kottke TJ, Blajeski AL, Martins LM, Mesner PW Jr, Davidson NE, Earnshaw WC, Armstrong DK, Kaufmann SH (1999) Comparison of paclitaxel-, 5-fluoro-2’-deoxyuridine-, and epidermal growth factor (EGF)-induced apoptosis. Evidence for EGF-induced anoikis. J Biol Chem 274:15927–15936
Krahn G, Leiter U, Kaskel P, Udart M, Utikal J, Bezold G, Peter RU (2001) Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Eur J Cancer 37:251–259
Kusewitt DF, Choi C, Newkirk KM, Leroy P, Li Y, Chavez MG, Hudson LG (2009) Slug/Snai2 is a downstream mediator of epidermal growth factor receptor-stimulated reepithelialization. J Invest Dermatol 129:491–495
Lechler T, Fuchs E (2005) Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437:275–280
Lewis DA, Zweig B, Hurwitz SA, Spandau DF (2003) Inhibition of erbB receptor family members protects HaCaT keratinocytes from ultraviolet-B-induced apoptosis. J Invest Dermatol 120:483–488
Ley KD, Ellem KA (1992) UVC modulation of epidermal growth factor receptor number in HeLa S3 cells. Carcinogenesis 13:183–187
Li S, Wang Q, Wang Y, Chen X, Wang Z (2009) PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration. Mol Endocrinol 23:901–913
Linardou H, Dahabreh IJ, Bafaloukos D, Kosmidis P, Murray S (2009) Somatic EGFR mutations and efficacy of tyrosine kinase inhibitors in NSCLC. Nat Rev Clin Oncol 6:352–366
Liu Y, Poon RT, Shao W, Sun X, Chen H, Kok TW, Fan ST (2007) Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma. Cancer Lett 248:32–40
Madson JG, Lynch DT, Tinkum KL, Putta SK, Hansen LA (2006) Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation. Am J Pathol 169:1402–1414
Maklad A, Nicolai JR, Bichsel KJ, Evenson JE, Lee TC, Threadgill DW, Hansen LA (2009) The EGFR Is Required for Proper Innervation to the Skin. J Invest Dermatol 129:690–698
Mariotti A, Kedeshian PA, Dans M, Curatola AM, Gagnoux-Palacios L, Giancotti FG (2001) EGF-R signaling through Fyn kinase disrupts the function of integrin alpha6beta4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion. J Cell Biol 155:447–458
Mascia F, Mariani V, Girolomoni G, Pastore S (2003) Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation. Am J Pathol 163:303–312
Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, Derynck R (1995) Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376:337–341
Minami S, Iwamoto R, Mekada E (2008) HB-EGF decelerates cell proliferation synergistically with TGFalpha in perinatal distal lung development. Dev Dyn 237:247–258
Modjtahedi H, Affleck K, Stubberfield C, Dean C (1998) EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5. Int J Oncol 13:335–342
Morris ZS, McClatchey AI (2009) Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma. Proc Natl Acad Sci USA 106:9767–9772
Murillas R, Larcher F, Conti CJ, Santos M, Ulrich A, Jorcano JL (1995) Expression of a dominant negative mutant of epidermal growth factor receptor in the epidermis of transgenic mice elicits striking alterations in hair follicle development and skin structure. EMBO J 14:5216–5223
Nakamura Y, Sotozono C, Kinoshita S (2001) The epidermal growth factor receptor (EGFR): role in corneal wound healing and homeostasis 5. Exp Eye Res 72:511–517
Nanney LB, Stoscheck CM, King LE Jr, Underwood RA, Holbrook KA (1990) Immunolocalization of epidermal growth factor receptors in normal developing human skin. J Invest Dermatol 94:742–748
Normanno N, De LA, Bianco C, Strizzi L, Mancino M, Maiello MR, Carotenuto A, De FG, Caponigro F, Salomon DS (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2–16
Ohtsu H, Dempsey PJ, Eguchi S (2006) ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am J Physiol Cell Physiol 291:C1–C10
Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (1999) ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J Biol Chem 274:17209–17218
Oliveira S, van Bergen en Henegouwen PM, Storm G, Schiffelers RM (2006) Molecular biology of epidermal growth factor receptor inhibition for cancer therapy. Expert Opin Biol Ther 6:605–617
Pastore S, Mascia F, Mariani V, Girolomoni G (2008) The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol 128:1365–1374
Pedersen MW, Meltorn M, Damstrup L, Poulsen HS (2001) The type III epidermal growth factor receptor mutation. Biological significance and potential target for anti-cancer therapy. Ann Oncol 12:745–760
Piepkorn M, Predd H, Underwood R, Cook P (2003) Proliferation-differentiation relationships in the expression of heparin-binding epidermal growth factor-related factors and erbB receptors by normal and psoriatic human keratinocytes. Arch Dermatol Res 295:93–101
Powell TJ, Ben-Bassat H, Klein BY, Chen H, Shenoy N, McCollough J, Narog B, Gazit A, Harzstark Z, Chaouat M, Levitzki R, Tang C, McMahon J, Shawver L, Levitzki A (1999) Growth inhibition of psoriatic keratinocytes by quinazoline tyrosine kinase inhibitors. Br J Dermatol 141:802–810
Radtke F, Raj K (2003) The role of Notch in tumorigenesis: oncogene or tumour suppressor? Nat Rev Cancer 3:756–767
Ren Z., Schaefer T.S. (2002). Erbs-s activates Stat3 alpha in a Src- and JAK2 dependent manner. J. Biol. Chem. 277:38486–38493
Repertinger SK, Campagnaro E, Fuhrman J, El Abaseri T, Yuspa SH, Hansen LA (2004) EGFR enhances early healing after cutaneous incisional wounding. J Invest Dermatol 123:982–989
Richardson GD, Bazzi H, Fantauzzo KA, Waters JM, Crawford H, Hynd P, Christiano AM, Jahoda CA (2009) KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin. Development 136:2153–2164
Rogers SJ, Harrington KJ, Rhys-Evans P, Charoenrat P, Eccles SA (2005) Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev 24:47–69
Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, Hartmann D, Saftig P, Blobel CP (2004) Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol 164:769–779
Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225
Schmidt E, Waschke J (2009) Apoptosis in pemphigus. Autoimmun Rev 8:533–537
Sheng G, Bernabe KQ, Guo J, Warner BW (2006) Epidermal growth factor receptor-mediated proliferation of enterocytes requires p21waf1/cip1 expression. Gastroenterology 131:153–164
Sheu JJ, Hua CH, Wan L, Lin YJ, Lai MT, Tseng HC, Jinawath N, Tsai MH, Chang NW, Lin CF, Lin CC, Hsieh LJ, Wang TL, Shih I, Tsai FJ (2009) Functional genomic analysis identified epidermal growth factor receptor activation as the most common genetic event in oral squamous cell carcinoma. Cancer Res 69:2568–2576
Shilo BZ (2005) Regulating the dynamics of EGF receptor signaling in space and time. Development 132:4017–4027
Shirakata Y, Komurasaki T, Toyoda H, Hanakawa Y, Yamasaki K, Tokumaru S, Sayama K, Hashimoto K (2000) Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes. J Biol Chem 275:5748–5753
Sibilia M, Fleischmann A, Behrens A, Stingl L, Carroll J, Watt FM, Schlessinger J, Wagner EF (2000) The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell 102:211–220
Sibilia M, Wagner EF (1995) Strain-dependent epithelial defects in mice lacking the EGF receptor. Science 269:234–238
Singer AJ, Clark RA (1999) Cutaneous wound healing4. N Engl J Med 341:738–746
Singh B, Schneider M, Knyazev P, Ullrich A (2009) UV-induced EGFR signal transactivation is dependent on proligand shedding by activated metalloproteases in skin cancer cell lines. Int J Cancer 124:531–539
Stoll SW, Johnson JL, Bhasin A, Johnston A, Gudjonsson JE, Rittie L, Elder JT (2009) Metalloproteinase-mediated, context-dependent function of amphiregulin and HB-EGF in human keratinocytes and skin. J Invest Dermatol 52:442–448
Stoll SW, Kansra S, Peshick S, Fry DW, Leopold WR, Wiesen JF, Sibilia M, Zhang T, Werb Z, Derynck R, Wagner EF, Elder JT (2001) Differential utilization and localization of ErbB receptor tyrosine kinases in skin compared to normal and malignant keratinocytes. Neoplasia 3:339–350
Strachan L, Murison JG, Prestidge RL, Sleeman MA, Watson JD, Kumble KD (2001) Cloning and biological activity of epigen, a novel member of the epidermal growth factor superfamily. J Biol Chem 276:18265–18271
Sundaram MV (2005) The love-hate relationship between Ras and Notch. Genes Dev 19:1825–1839
Swindle CS, Tran KT, Johnson TD, Banerjee P, Mayes AM, Griffith L, Wells A (2001) Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor. J Cell Biol 154:459–468
Takamune Y, Ikebe T, Nagano O, Nakayama H, Ota K, Obayashi T, Saya H, Shinohara M (2007) ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell carcinoma. Virchows Arch 450:169–177
Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC, Barnard JA, Yuspa SH, Coffey RJ, Magnuson T (1995) Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 269:230–234
Tzahar E, Moyer JD, Waterman H, Barbacci EG, Bao J, Levkowitz G, Shelly M, Strano S, Pinkas-Kramarski R, Pierce JH, Andrews GC, Yarden Y (1998) Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network. EMBO J 17:5948–5963
Varani J, Kang S, Stoll S, Elder JT (1998) Human psoriatic skin in organ culture: comparison with normal skin exposed to exogenous growth factors and effects of an antibody to the EGF receptor. Pathobiology 66:253–259
Vincent A, Van SI (2009) Epigenetics, stem cells and epithelial cell fate. Differentiation 78(2–3):99–107
Visco V, Belleudi F, Marchese C, Leone L, Aimati L, Cardinali G, Kovacs D, Frati L, Torrisi MR (2004) Differential response to keratinocyte growth factor receptor and epidermal growth factor receptor ligands of proliferating and differentiating intestinal epithelial cells. J Cell Physiol 200:31–44
Wan YS, Wang ZQ, Shao Y, Voorhees JJ, Fisher GJ (2001) Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. Int J Oncol 18:461–466
Watanabe T, Shintani A, Nakata M, Shing Y, Folkman J, Igarashi K, Sasada R (1994) Recombinant human betacellulin. Molecular structure, biological activities, and receptor interaction. J Biol Chem 269:9966–9973
Weijzen S, Rizzo P, Braid M, Vaishnav R, Jonkheer SM, Zlobin A, Osborne BA, Gottipati S, Aster JC, Hahn WC, Rudolf M, Siziopikou K, Kast WM, Miele L (2002) Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med 8:979–986
Werner S, Grose R (2003) Regulation of wound healing by growth factors and cytokines1. Physiol Rev 83:835–870
Woodworth CD, Michael E, Marker D, Allen S, Smith L, Nees M (2005) Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment. Mol Cancer Ther 4:650–658
Xie H, Pallero MA, Gupta K, Chang P, Ware MF, Witke W, Kwiatkowski DJ, Lauffenburger DA, Murphy-Ullrich JE, Wells A (1998) EGF receptor regulation of cell motility: EGF induces disassembly of focal adhesions independently of the motility-associated PLCgamma signaling pathway. J Cell Sci 111(Pt 5):615–624
Xu Y, Shao Y, Voorhees JJ, Fisher GJ (2006) Oxidative inhibition of receptor-type protein-tyrosine phosphatase kappa by ultraviolet irradiation activates epidermal growth factor receptor in human keratinocytes. J Biol Chem 281:27389–27397
Yang Z, Bagheri-Yarmand R, Wang RA, Adam L, Papadimitrakopoulou VV, Clayman GL, El-Naggar A, Lotan R, Barnes CJ, Hong WK, Kumar R (2004) The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) suppresses c-Src and Pak1 pathways and invasiveness of human cancer cells. Clin Cancer Res 10:658–667
Yarden Y, Shilo BZ (2007) SnapShot: EGFR signaling pathway. Cell 131:1018
Yasmeen A, Bismar TA, Al Moustafa AE (2006) ErbB receptors and epithelial-cadherin-catenin complex in human carcinomas. Future Oncol 2:765–781
Yoshida A, Kanno H, Watabe D, Akasaka T, Sawai T (2008) The role of heparin-binding EGF-like growth factor and amphiregulin in the epidermal proliferation of psoriasis in cooperation with TNFalpha. Arch Dermatol Res 300:37–45
Zahorowska B, Crowe PJ, Yang JL (2009) Combined therapies for cancer: a review of EGFR-targeted monotherapy and combination treatment with other drugs. J Cancer Res Clin Oncol 135:1137–1148
Zorzou MP, Stratigos A, Efstathiou E, Bamias A (2004) Exacerbation of psoriasis after treatment with an EGFR tyrosine kinase inhibitor. Acta Derm Venereol 84:308–309
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Repertinger, S.K., Madson, J.G., Bichsel, K.J., Hansen, L.A. (2011). The Epidermal Growth Factor Receptor in Normal and Neoplastic Epithelia. In: Glick, A., Waes, C. (eds) Signaling Pathways in Squamous Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7203-3_5
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