Landscape of EGFR signaling network in human cancers: Biology and therapeutic response in relation to receptor subcellular locations

Cancer Letters

Volumn 318, Issue 2, 2012, Pages 124-134

  Han, Woody ^a   Lo, Hui Wen ^a,b  

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b DUKE CANCER INSTITUTE   (United States)

Author keywords

Apoptosis; Cancer; EGFR; EGFRvIII; Gene regulation; HER2; Proliferation; Radioresistance; Survival

Indexed keywords

CAPECITABINE; CELECOXIB; CETUXIMAB; DASATINIB; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; GEFITINIB; GEMCITABINE; IRINOTECAN; LAPATINIB; LETROZOLE; PANITUMUMAB; PROTEIN TYROSINE KINASE; RAPAMYCIN; TRASTUZUMAB; VASCULOTROPIN RECEPTOR;

APOPTOSIS; BREAST CANCER; CANCER CELL; CANCER PATIENT; CANCER RADIOTHERAPY; CELL MIGRATION; CELL NUCLEUS; COLORECTAL CANCER; DNA REPAIR; DRUG EFFICACY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; HEAD AND NECK CARCINOMA; HUMAN; LIGAND BINDING; LUNG NON SMALL CELL CANCER; MALIGNANT NEOPLASTIC DISEASE; MITOCHONDRION; MOLECULAR BIOLOGY; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROGNOSIS; PROTEIN FUNCTION; SHORT SURVEY; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; TREATMENT RESPONSE;

EID: 84858156041     PISSN: 03043835     EISSN: 18727980     Source Type: Journal    
DOI: 10.1016/j.canlet.2012.01.011     Document Type: Review

References (144)

1. Cohen S., Carpenter G., King L. Epidermal growth factor-receptor-protein kinase interactions. Co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J Biol Chem 1980, 255:4834-4842.
2. Cohen S., Ushiro H., Stoscheck C., Chinkers M. A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles. J Biol Chem 1982, 257:1523-1531.
3. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 1962, 237:1555-1562.
4. Cohen S., Carpenter G., King L. Epidermal growth factor-receptor-protein kinase interactions. Prog Clin Biol Res 1981, 66 Pt A:557-567.
5. Cohen S., Fava R.A., Sawyer S.T. Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver. Proc Natl Acad Sci U S A 1982, 79:6237-6241.
6. Sporn M.B., Todaro G.J. Autocrine secretion and malignant transformation of cells. N Engl J Med 1980, 303:878-880.
7. Lo H.W., Hung M.C. Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br J Cancer 2006, 94:184-188.
8. Yarden Y., Shilo B.Z. SnapShot: EGFR signaling pathway. Cell 2007, 131:1018.
9. Lo H.W. EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug resistance. Current molecular pharmacology 2010, 3:37-52.
10. Yamazaki H., Ohba Y., Tamaoki N., Shibuya M. A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors. Jpn J Cancer Res 1990, 81:773-779.
11. Ekstrand A.J., Sugawa N., James C.D., Collins V.P. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci U S A 1992, 89:4309-4313.
12. Wong A.J., Ruppert J.M., Bigner S.H., Grzeschik C.H., Humphrey P.A., Bigner D.S., Vogelstein B. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A 1992, 89:2965-2969.
13. Sugawa N., Ekstrand A.J., James C.D., Collins V.P. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A 1990, 87:8602-8606.
14. van den Bent M.J., Brandes A.A., Rampling R., Kouwenhoven M.C., Kros J.M., Carpentier A.F., Clement P.M., Frenay M., Campone M., Baurain J.F., Armand J.P., Taphoorn M.J., Tosoni A., Kletzl H., Klughammer B., Lacombe D., Gorlia T. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 2009, 27:1268-1274.
15. Reardon D.A., Desjardins A., Vredenburgh J.J., Gururangan S., Friedman A.H., Herndon J.E., Marcello J., Norfleet J.A., McLendon R.E., Sampson J.H., Friedman H.S. Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma. J Neurooncol 2009.
16. Brand T.M., Iida M., Wheeler D.L. Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol. Ther. 2011, 11:777-792.
17. Paez J.G., Janne P.A., Lee J.C., Tracy S., Greulich H., Gabriel S., Herman P., Kaye F.J., Lindeman N., Boggon T.J., Naoki K., Sasaki H., Fujii Y., Eck M.J., Sellers W.R., Johnson B.E., Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004, 304:1497-1500.
18. Lynch T.J., Bell D.W., Sordella R., Gurubhagavatula S., Okimoto R.A., Brannigan B.W., Harris P.L., Haserlat S.M., Supko J.G., Haluska F.G., Louis D.N., Christiani D.C., Settleman J., Haber D.A. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004, 350:2129-2139.
19. Mitsudomi T., Morita S., Yatabe Y., Negoro S., Okamoto I., Tsurutani J., Seto T., Satouchi M., Tada H., Hirashima T., Asami K., Katakami N., Takada M., Yoshioka H., Shibata K., Kudoh S., Shimizu E., Saito H., Toyooka S., Nakagawa K., Fukuoka M. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. The lancet oncology 2010, 11:121-128.
20. Bonanno L., Jirillo A., Favaretto A. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors and new therapeutic perspectives in non small cell lung cancer. Curr Drug Targets 2011, 12:922-933.
21. Nguyen K.S., Kobayashi S., Costa D.B. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 2009, 10:281-289.
22. Pao W., Miller V.A., Politi K.A., Riely G.J., Somwar R., Zakowski M.F., Kris M.G., Varmus H. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005, 2:e73.
23. Ogino A., Kitao H., Hirano S., Uchida A., Ishiai M., Kozuki T., Takigawa N., Takata M., Kiura K., Tanimoto M. Emergence of epidermal growth factor receptor T790M mutation during chronic exposure to gefitinib in a non small cell lung cancer cell line. Cancer Res 2007, 67:7807-7814.
24. Bell D.W., Gore I., Okimoto R.A., Godin-Heymann N., Sordella R., Mulloy R., Sharma S.V., Brannigan B.W., Mohapatra G., Settleman J., Haber D.A. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005, 37:1315-1316.
25. Engelman J.A., Janne P.A. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res 2008, 14:2895-2899.
26. Beau-Faller M., Ruppert A.M., Voegeli A.C., Neuville A., Meyer N., Guerin E., Legrain M., Mennecier B., Wihlm J.M., Massard G., Quoix E., Oudet P., Gaub M.P. MET gene copy number in non-small cell lung cancer: molecular analysis in a targeted tyrosine kinase inhibitor naive cohort. J Thorac Oncol 2008, 3:331-339.
27. Arteaga C.L. HER3 and mutant EGFR meet MET. Nat Med 2007, 13:675-677.
28. Engelman J.A., Zejnullahu K., Mitsudomi T., Song Y., Hyland C., Park J.O., Lindeman N., Gale C.M., Zhao X., Christensen J., Kosaka T., Holmes A.J., Rogers A.M., Cappuzzo F., Mok T., Lee C., Johnson B.E., Cantley L.C., Janne P.A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007, 316:1039-1043.
29. Morgillo F., Kim W.Y., Kim E.S., Ciardiello F., Hong W.K., Lee H.Y. Implication of the insulin-like growth factor-IR pathway in the resistance of non-small cell lung cancer cells to treatment with gefitinib. Clin Cancer Res 2007, 13:2795-2803.
30. Ramalingam S.S., Spigel D.R., Chen D., Steins M.B., Engelman J.A., Schneider C.P., Novello S., Eberhardt W.E., Crino L., Habben K., Liu L., Janne P.A., Brownstein C.M., Reck M. Randomized Phase II Study of Erlotinib in Combination With Placebo or R1507, a Monoclonal Antibody to Insulin-Like Growth Factor-1 Receptor, for Advanced-Stage Non-Small-Cell Lung Cancer. J Clin Oncol 2011, 29:4574-4580.
31. Lo H.W. EGFR-targeted Cancer Therapy: Promise. Problems and Potential Solutions Translational Medicine 2011, 1. 10.4172/2161-1025.1000105e.
32. Coker K.J., Staros J.V., Guyer C.A. A kinase-negative epidermal growth factor receptor that retains the capacity to stimulate DNA synthesis. Proc Natl Acad Sci U S A 1994, 91:6967-6971.
33. Deb T.B., Su L., Wong L., Bonvini E., Wells A., David M., Johnson G.R. Epidermal growth factor (EGF) receptor kinase-independent signaling by EGF. J Biol Chem 2001, 276:15554-15560.
34. Ewald J.A., Wilkinson J.C., Guyer C.A., Staros J.V. Ligand- and kinase activity-independent cell survival mediated by the epidermal growth factor receptor expressed in 32D cells. Exp Cell Res 2003, 282:121-131.
35. Weihua Z., Tsan R., Huang W.C., Wu Q., Chiu C.H., Fidler I.J., Hung M.C. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer cell 2008, 13:385-393.
36. Zhu H., Cao X., Ali-Osman F., Keir S., Lo H.W. EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity. Cancer Lett 2010, 294:101-110.
37. Irwin M.E., Bohin N., Boerner J.L. Src family kinases mediate epidermal growth factor receptor signaling from lipid rafts in breast cancer cells. Cancer Biol Ther 2011, 12:718-726.
38. Irwin M.E., Mueller K.L., Bohin N., Ge Y., Boerner J.L. Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J Cell Physiol 2011, 226:2316-2328.
39. Hung M.C., Link W. Protein localization in disease and therapy. J. Cell Sci. 2011, 124:3381-3392.
40. Wang Y.N., Yamaguchi H., Hsu J.M., Hung M.C. Nuclear trafficking of the epidermal growth factor receptor family membrane proteins. Oncogene 2010, 29:3997-4006.
41. Lo H.W. Nuclear mode of the EGFR signaling network: biology, prognostic value, and therapeutic implications. Discov Med 2010, 10:44-51.
42. Carpenter G., Liao H.J. Trafficking of receptor tyrosine kinases to the nucleus. Exp Cell Res 2009, 315:1556-1566.
43. Wheeler D.L., Dunn E.F., Harari P.M. Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat Rev Clin Oncol 2010, 7:493-507.
44. Anderson D., Koch C.A., Grey L., Ellis C., Moran M.F., Pawson T. Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors. Science 1990, 250:979-982.
45. Navolanic P.M., Steelman L.S., McCubrey J.A. EGFR family signaling and its association with breast cancer development and resistance to chemotherapy (Review). Int J Oncol 2003, 22:237-252.
46. Park O.K., Schaefer T.S., Nathans D. In vitro activation of Stat3 by epidermal growth factor receptor kinase. Proc Natl Acad Sci U S A 1996, 93:13704-13708.
47. Bowman T., Garcia R., Turkson J., Jove R. STATs in oncogenesis. Oncogene 2000, 19:2474-2488.
48. Bowman T., Broome M.A., Sinibaldi D., Wharton W., Pledger W.J., Sedivy J.M., Irby R., Yeatman T., Courtneidge S.A., Jove R. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci U S A 2001, 98:7319-7324.
49. Barre B., Avril S., Coqueret O. Opposite regulation of myc and p21waf1 transcription by STAT3 proteins. J Biol Chem 2003, 278:2990-2996.
50. Lo H.W., Cao X., Zhu H., Ali-Osman F. Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clin Cancer Res 2008, 14:6042-6054.
51. Lo H.W., Hsu S.C., Xia W., Cao X., Shih J.Y., Wei Y., Abbruzzese J.L., Hortobagyi G.N., Hung M.C. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res 2007, 67:9066-9076.
52. Bacus S.S., Chin D., Yarden Y., Zelnick C.R., Stern D.F. Type 1 receptor tyrosine kinases are differentially phosphorylated in mammary carcinoma and differentially associated with steroid receptors. Am J Pathol 1996, 148:549-558.
53. Craven R.J., Lightfoot H., Cance W.G. A decade of tyrosine kinases: from gene discovery to therapeutics. Surg Oncol 2003, 12:39-49.
54. Baselga J., Norton L. Focus on breast cancer. Cancer Cell 2002, 1:319-322.
55. Bromberg J.F., Wrzeszczynska M.H., Devgan G., Zhao Y., Pestell R.G., Albanese C., Darnell J.E. Stat3 as an oncogene. Cell 1999, 98:295-303.
56. Miettinen P.J., Berger J.E., Meneses J., Phung Y., Pedersen R.A., Werb Z., Derynck R. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 1995, 376:337-341.
57. Luetteke N.C., Phillips H.K., Qiu T.H., Copeland N.G., Earp H.S., Jenkins N.A., Lee D.C. The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase. Genes Dev 1994, 8:399-413.
58. Hanabata Y., Nakajima Y., Morita K.I., Kayamori K., Omura K. Coexpression of SGLT1 and EGFR is associated with tumor differentiation in oral squamous cell carcinoma. Odontology 2011.
59. Chen L., Willis S.N., Wei A., Smith B.J., Fletcher J.I., Hinds M.G., Colman P.M., Day C.L., Adams J.M., Huang D.C. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 2005, 17:393-403.
60. Chipuk J.E., Fisher J.C., Dillon C.P., Kriwacki R.W., Kuwana T., Green D.R. Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:20327-20332.
61. Gallenne T., Gautier F., Oliver L., Hervouet E., Noel B., Hickman J.A., Geneste O., Cartron P.-F., Vallette F.M., Manon S., Juin P. Bax activation by the BH3-only protein Puma promotes cell dependence on antiapoptotic Bcl-2 family members. J. Cell Biol. 2009, 185:279-290.
62. Kim H., Tu H.C., Ren D., Takeuchi O., Jeffers J.R., Zambetti G.P., Hsieh J.J., Cheng E.H. Stepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis. Mol Cell 2009, 36:487-499.
63. Yu J., Zhang L., Hwang P.M., Kinzler K.W., Vogelstein B. PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 2001, 7:673-682.
64. Yu J., Wang Z., Kinzler K.W., Vogelstein B., Zhang L. PUMA mediates the apoptotic response to p53 in colorectal cancer cells. Proceedings of the National Academy of Sciences of the United States of America 2003, 100:1931-1936.
65. Ito H., Kanzawa T., Miyoshi T., Hirohata S., Kyo S., Iwamaru A., Aoki H., Kondo Y., Kondo S. Therapeutic efficacy of PUMA for malignant glioma cells regardless of p53 status. Human gene therapy 2005, 16:685-698.
66. Liu D., Ou L., Clemenson G.D., Chao C., Lutske M.E., Zambetti G.P., Gage F.H., Xu Y. Puma is required for p53-induced depletion of adult stem cells. Nature cell biology 2010, 12:993-998.
67. Marti U., Burwen S.J., Wells A., Barker M.E., Huling S., Feren A.M., Jones A.L. Localization of epidermal growth factor receptor in hepatocyte nuclei. Hepatology 1991, 13:15-20.
68. Raper S.E., Burwen S.J., Barker M.E., Jones A.L. Translocation of epidermal growth factor to the hepatocyte nucleus during rat liver regeneration. Gastroenterology 1987, 92:1243-1250.
69. Schausberger E., Eferl R., Parzefall W., Chabicovsky M., Breit P., Wagner E.F., Schulte-Hermann R., Grasl-Kraupp B., Chabikovsky M. Induction of DNA synthesis in primary mouse hepatocytes is associated with nuclear pro-transforming growth factor alpha and erbb-1 and is independent of c-jun. Carcinogenesis 2003, 24:835-841.
70. Lin S.Y., Makino K., Xia W., Matin A., Wen Y., Kwong K.Y., Bourguignon L., Hung M.C. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 2001, 3:802-808.
71. Lo H.-W., Hsu S.-C., Ali-Seyed M., Gunduz M., Xia W., Wei Y., Bartholomeusz G., Shih J.-Y., Hung M.-C. Nuclear Interaction of EGFR and STAT3 in the Activation of iNOS/NO Pathway. Cancer Cell 2005, 7:575-589.
72. Marti U., Ruchti C., Kampf J., Thomas G.A., Williams E.D., Peter H.J., Gerber H., Burgi U. Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues. Thyroid 2001, 11:137-145.
73. Cao H., Lei Z.M., Bian L., Rao C.V. Functional nuclear epidermal growth factor receptors in human choriocarcinoma JEG-3 cells and normal human placenta. Endocrinology 1995, 136:3163-3172.
74. Lo H.W., Xia W., Wei Y., Ali-Seyed M., Huang S.F., Hung M.C. Novel prognostic value of nuclear epidermal growth factor receptor in breast cancer. Cancer Res 2005, 65:338-348.
75. Kim J., Jahng W.J., Di Vizio D., Lee J.S., Jhaveri R., Rubin M.A., Shisheva A., Freeman M.R. The Phosphoinositide Kinase PIKfyve Mediates Epidermal Growth Factor Receptor Trafficking to the Nucleus. Cancer Res 2007, 67:9229-9237.
76. Hanada N., Lo H.W., Day C.P., Pan Y., Nakajima Y., Hung M.C. Co-regulation of B-Myb expression by E2F1 and EGF receptor. Mol Carcinog 2006, 45:10-17.
77. Xia W., Wei Y., Du Y., Liu J., Chang B., Yu Y.L., Huo L.F., Miller S., Hung M.C. Nuclear expression of epidermal growth factor receptor is a novel prognostic value in patients with ovarian cancer. Mol Carcinog 2009, 48:610-617.
78. Psyrri A., Yu Z., Weinberger P.M., Sasaki C., Haffty B., Camp R., Rimm D., Burtness B.A. Quantitative determination of nuclear and cytoplasmic epidermal growth factor receptor expression in oropharyngeal squamous cell cancer by using automated quantitative analysis. Clin Cancer Res 2005, 11:5856-5862.
79. Li C., Iida M., Dunn E.F., Ghia A.J., Wheeler D.L. Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene 2009, 28:3801-3813.
80. Jaganathan S., Yue P.B., Paladino D.C., Bogdanovic J., Huo Q., Turkson J., Receptor A Functional Nuclear Epidermal Growth Factor Src and Stat3 Heteromeric Complex in Pancreatic Cancer Cells. PLoS One 2011, 6.
81. de la Iglesia N., Konopka G., Puram S.V., Chan J.A., Bachoo R.M., You M.J., Levy D.E., Depinho R.A., Bonni A. Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway. Genes Dev 2008, 22:449-462.
82. Lo H.W., Cao X., Zhu H., Ali-Osman F. Cyclooxygenase-2 is a novel transcriptional target of the nuclear EGFR-STAT3 and EGFRvIII-STAT3 signaling axes. Mol Cancer Res 2010, 8:232-245.
83. Liao H.J., Carpenter G. Role of the Sec61 translocon in EGF receptor trafficking to the nucleus and gene expression. Mol Biol Cell 2007, 18:1064-1072.
84. Lo H.W., Ali-Seyed M., Wu Y., Bartholomeusz G., Hsu S.C., Hung M.C. Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin beta1 and CRM1. J Cell Biochem 2006, 98:1570-1583.
85. Klein C., Gensburger C., Freyermuth S., Nair B.C., Labourdette G., Malviya A.N. A 120 kDa nuclear phospholipase Cgamma1 protein fragment is stimulated in vivo by EGF signal phosphorylating nuclear membrane EGFR. Biochemistry 2004, 43:15873-15883.
86. Edwards J., Traynor P., Munro A.F., Pirret C.F., Dunne B., Bartlett J.M. The role of HER1-HER4 and EGFRvIII in hormone-refractory prostate cancer. Clin Cancer Res 2006, 12:123-130.
87. Eldredge E.R., Korf G.M., Christensen T.A., Connolly D.C., Getz M.J., Maihle N.J. Activation of c-fos gene expression by a kinase-deficient epidermal growth factor receptor. Mol Cell Biol 1994, 14:7527-7534.
88. Xie Y., Hung M.C. Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation. Biochem Biophys Res Commun 1994, 203:1589-1598.
89. Hung L.Y., Tseng J.T., Lee Y.C., Xia W., Wang Y.N., Wu M.L., Chuang Y.H., Lai C.H., Chang W.C. Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression. Nucleic Acids Res 2008, 36:4337-4351.
90. Huang W.C., Chen Y.J., Li L.Y., Wei Y.L., Hsu S.C., Tsai S.L., Chiu P.C., Huang W.P., Wang Y.N., Chen C.H., Chang W.C., Chen A.J.E., Tsai C.H., Hung M.C. Nuclear Translocation of Epidermal Growth Factor Receptor by Akt-dependent Phosphorylation Enhances Breast Cancer-resistant Protein Expression in Gefitinib-resistant Cells. Journal of Biological Chemistry 2011, 286:20558-20568.
91. Huo L., Wang Y.N., Xia W., Hsu S.C., Lai C.C., Li L.Y., Chang W.C., Wang Y., Hsu M.C., Yu Y.L., Huang T.H., Ding Q., Chen C.H., Tsai C.H., Hung M.C. RNA helicase A is a DNA-binding partner for EGFR-mediated transcriptional activation in the nucleus. Proc Natl Acad Sci U S A 2010, 107:16125-16130.
92. Bitler B.G., Goverdhan A., Schroeder J.A. MUC1 regulates nuclear localization and function of the epidermal growth factor receptor. J. Cell Sci. 2010, 123:1716-1723.
93. Wang S.C., Lien H.C., Xia W., Chen I.F., Lo H.W., Wang Z., Ali-Seyed M., Lee D.F., Bartholomeusz G., Ou-Yang F., Giri D.K., Hung M.C. Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2. Cancer Cell 2004, 6:251-261.
94. Beguelin W., Flaque M.C.D., Proietti C.J., Cayrol F., Rivas M.A., Tkach M., Rosemblit C., Tocci J.M., Charreau E.H., Schillaci R., Elizalde P.V. Progesterone Receptor Induces ErbB-2 Nuclear Translocation To Promote Breast Cancer Growth via a Novel Transcriptional Effect: ErbB-2 Function as a Coactivator of Stat3. Molecular and Cellular Biology 2010, 30:5456-5472.
95. Li L.Y., Chen H.Y., Hsieh Y.H., Wang Y.N., Chu H.J., Chen Y.H., Chien P.J., Ma H.T., Tsai H.C., Lai C.C., Sher Y.P., Lien H.C., Tsai C.H., Hung M.C. Nuclear ErbB2 Enhances Translation and Cell Growth by Activating Transcription of Ribosomal RNA Genes. Cancer Research 2011, 71:4269-4279.
96. Wang S.C., Nakajima Y., Yu Y.L., Xia W., Chen C.T., Yang C.C., McIntush E.W., Li L.Y., Hawke D.H., Kobayashi R., Hung M.C. Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol 2006, 8:1359-1368.
97. Dittmann K., Mayer C., Fehrenbacher B., Schaller M., Raju U., Milas L., Chen D.J., Kehlbach R., Rodemann H.P. Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. J Biol Chem 2005, 280:31182-31189.
98. Dittmann K., Mayer C., Rodemann H.P. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol 2005, 76:157-161.
99. Klaus H.D., Mayer C., Petra A.O., Raju U., Nickolaus H.A., Luka M., Rodemann H.P. Celecoxib induced tumor cell radiosensitization by inhibiting radiation induced nuclear EGFR transport and DNA-repair: A COX-2 independent mechanism. Int. J. Radiat. Oncol. Biol. Phys. 2008, 70:203-212.
100. Hsu S.C., Miller S.A., Wang Y., Hung M.C. Nuclear EGFR is required for cisplatin resistance and DNA repair. American journal of translational research 2009, 1:249-258.
101. Liccardi G., Hartley J.A., Hochhauser D. EGFR Nuclear Translocation Modulates DNA Repair following Cisplatin and Ionizing Radiation Treatment. Cancer Research 2011, 71:1103-1114.
102. Luo B., Yu S.Y., Zhuang L., Xia S., Zhao Z., Rong L. Induction of ERBB2 Nuclear Transport after Radiation in Breast Cancer Cells. J. Huazhong Univ. Sci. Tech.-Med. 2009, 29:350-353.
103. Xu Y.R., Shao Y., Zhou J., Voorhees J.J., Fisher G.J. Ultraviolet Irradiation-Induces Epidermal Growth Factor Receptor (EGFR) Nuclear Translocation in Human Keratinocytes. J. Cell. Biochem. 2009, 107:873-880.
104. Dittmann K., Mayer C., Kehlbach R., Rodemann H.P. The radioprotector Bowman-Birk proteinase inhibitor stimulates DNA repair via epidermal growth factor receptor phosphorylation and nuclear transport. Radiotherapy and Oncology 2008, 86:375-382.
105. Wanner G., Mayer C., Kehlbach R., Rodemann H.P., Dittmann K. Activation of protein kinase Cepsilon stimulates DNA-repair via epidermal growth factor receptor nuclear accumulation. Radiother Oncol 2008, 86:383-390.
106. Moy B., Kirkpatrick P., Kar S., Goss P. Lapatinib. Nature reviews 2007, 6:431-432.
107. Patel D., Lahiji A., Patel S., Franklin M., Jimenez X., Hicklin D.J., Kang X. Monoclonal antibody cetuximab binds to and down-regulates constitutively activated epidermal growth factor receptor vIII on the cell surface. Anticancer Res 2007, 27:3355-3366.
108. Rivera F., Vega-Villegas M.E., Lopez-Brea M.F., Marquez R. Current situation of Panitumumab, Matuzumab, Nimotuzumab and Zalutumumab. Acta oncologica (Stockholm, Sweden) 2008, 47:9-19.
109. Dittmann K., Mayer C., Fehrenbacher B., Schaller M., Kehlbach R., Rodemann H.P. Nuclear EGFR shuttling induced by ionizing radiation is regulated by phosphorylation at residue Thr654. FEBS Lett. 2010, 584:3878-3884.
110. Kim H.P., Yoon Y.K., Kim J.W., Han S.W., Hur H.S., Park J., Lee J.H., Oh D.Y., Im S.A., Bang Y.J., Kim T.Y. Lapatinib, a Dual EGFR and HER2 Tyrosine Kinase Inhibitor, Downregulates Thymidylate Synthase by Inhibiting the Nuclear Translocation of EGFR and HER2. PLoS One 2009, 4:9.
111. Liao H.J., Carpenter G. Cetuximab/C225-induced intracellular trafficking of epidermal growth factor receptor. Cancer Res 2009, 69:6179-6183.
112. Hadzisejdic I., Mustac E., Jonjic N., Petkovic M., Grahovac B. Nuclear EGFR in ductal invasive breast cancer: correlation with cyclin-D1 and prognosis. Mod. Pathol. 2010, 23:392-403.
113. Campos A.C.D., Rodrigues M.A., de Andrade C., de Goes A.M., Nathanson M.H., Gomes D.A. Epidermal growth factor receptors destined for the nucleus are internalized via a clathrin-dependent pathway. Biochemical and Biophysical Research Communications 2011, 412:341-346.
114. Grant B.D., Donaldson J.G. Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 2009, 10:597-608.
115. Ceresa B.P. Regulation of EGFR endocytic trafficking by rab proteins. Histol Histopathol 2006, 21:987-993.
116. Ceresa B.P., Bahr S.J. Rab7 activity affects epidermal growth factor:epidermal growth factor receptor degradation by regulating endocytic trafficking from the late endosome. J Biol Chem 2006, 281:1099-1106.
117. Giri D.K., Ali-Seyed M., Li L.-Y., Lee D.-F., Ling P., Bartholomeusz G., Wang S.-C., Hung M.-C. Endosomal Transport of ErbB-2: Mechanism for Nuclear Entry of the Cell Surface Receptor. Mol. Cell. Biol. 2005, 25:11005-11018.
118. Weis K. Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell 2003, 112:441-451.
119. Hsu S.C., Hung M.C. Characterization of a novel tripartite nuclear localization sequence in the EGFR family. J Biol Chem 2007, 282:10432-10440.
120. Wang Y.N., Wang H.M., Yamaguchi H., Lee H.J., Lee H.H., Hung M.C. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport. Biochemical and Biophysical Research Communications 2010, 399:498-504.
121. Wang Y.N., Yamaguchi H., Huo L.F., Du Y., Lee H.J., Lee H.H., Wang H.M., Hsu J.M., Hung M.C. The Translocon Sec61 beta Localized in the Inner Nuclear Membrane Transports Membrane-embedded EGF Receptor to the Nucleus. Journal of Biological Chemistry 2010, 285:38720-38729.
122. Wang Z.H., Tian X.X., Cheng Y., Yam G.H., Ng H.K., Ding M.X., Chew-Cheng S.B., Chew E.C. Association of EGFR gene fragments with nuclear matrices in glioblastoma cell lines. Anticancer Res 1998, 18:4329-4332.
123. Offterdinger M., Schofer C., Weipoltshammer K., Grunt T.W. C-erbB-3: a nuclear protein in mammary epithelial cells. J Cell Biol 2002, 157:929-939.
124. Tao Y., Song X., Tan Y., Lin X., Zhao Y., Zeng L., Tang M., Li W., Wu Q., Cao Y. Nuclear translocation of EGF receptor regulated by Epstein-Barr virus encoded latent membrane protein 1. Sci China C Life Sci 2004, 47:258-267.
125. Boerner J.L., Demory M.L., Silva C., Parsons S.J. Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II. Mol Cell Biol 2004, 24:7059-7071.
126. Demory M.L., Boerner J.L., Davidson R., Faust W., Miyake T., Lee I., Hüttemann M., Douglas R., Haddad G., Parsons S.J. Epidermal Growth Factor Receptor Translocation to the Mitochondria. Journal of Biological Chemistry 2009, 284:36592-36604.
127. Yao Y., Wang G., Li Z., Yan B., Guo Y., Jiang X., Xi Z. Mitochondrially localized EGFR is independent of its endocytosis and associates with cell viability. Acta Biochim Biophys Sin (Shanghai) 2010, 42:763-770.
128. Yue X., Song W., Zhang W., Chen L., Xi Z., Xin Z., Jiang X. Mitochondrially localized EGFR is subjected to autophagic regulation and implicated in cell survival. Autophagy 2008, 4:641-649.
129. Cao X., Zhu H., Ali-Osman F., Lo H.W. EGFR and EGFRvIII undergo stress- and EGFR kinase inhibitor-induced mitochondrial translocalization: a potential mechanism of EGFR-driven antagonism of apoptosis. Mol Cancer 2011, 10:26.
130. Dreier A., Barth S., Goswami A., Weis J. Cetuximab induces mitochondrial translocalization of EGFRvIII, but not EGFR: involvement of mitochondria in tumor drug resistance?. Tumour Biol 2011.
131. Naresh A., Long W., Vidal G.A., Wimley W.C., Marrero L., Sartor C.I., Tovey S., Cooke T.G., Bartlett J.M.S., Jones F.E. The ERBB4/HER4 Intracellular Domain 4ICD Is a BH3-Only Protein Promoting Apoptosis of Breast Cancer Cells. Cancer Res 2006, 66:6412-6420.
132. Naresh A., Thor A.D., Edgerton S.M., Torkko K.C., Kumar R., Jones F.E. The HER4/4ICD Estrogen Receptor Coactivator and BH3-Only Protein Is an Effector of Tamoxifen-Induced Apoptosis. Cancer Res 2008, 68:6387-6395.
133. Maher P.A. Nuclear Translocation of fibroblast growth factor (FGF) receptors in response to FGF-2. J Cell Biol 1996, 134:529-536.
134. Ni C.Y., Murphy M.P., Golde T.E., Carpenter G. Gamma -Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 2001, 294:2179-2181.
135. Ni C.Y., Yuan H., Carpenter G. Role of the ErbB-4 carboxyl terminus in gamma-secretase cleavage. J Biol Chem 2003, 278:4561-4565.
136. Raabe T.D., Deadwyler G., Varga J.W., Devries G.H. Localization of neuregulin isoforms and erbB receptors in myelinating glial cells. Glia 2004, 45:197-207.
137. Rakowicz-Szulczynska E.M., Herlyn M., Koprowski H. Nerve growth factor receptors in chromatin of melanoma cells, proliferating melanocytes, and colorectal carcinoma cells in vitro. Cancer Res 1988, 48:7200-7206.
138. Wells A., Marti U. Signalling shortcuts: cell-surface receptors in the nucleus?. Nat Rev Mol Cell Biol 2002, 3:697-702.
139. Pillai G., Cook N., Turley H., Leek R.D., Blasquez C., Pezzella F., Harris A.L., Gatter K.C. The expression and cellular localization of phosphorylated VEGFR2 in lymphoma and non-neoplastic lymphadenopathy: an immunohistochemical study. Histopathology 2005, 46:209-216.
140. Zwaagstra J.C., Guimond A., O'Connor-McCourt M.D. Predominant intracellular localization of the type I transforming growth factor-beta receptor and increased nuclear accumulation after growth arrest. Exp Cell Res 2000, 258:121-134.
141. Jans D.A., Hassan G. Nuclear targeting by growth factors, cytokines, and their receptors: a role in signaling?. Bioessays 1998, 20:400-411.
142. Tseng H.C., Lyu P.C., Lin W.C. Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain. BMC Cell Biol 2010, 11:48.
143. Fiorillo A.A., Medler T.R., Feeney Y.B., Liu Y., Tommerdahl K.L., Clevenger C.V. HMGN2 Inducibly Binds a Novel Transactivation Domain in Nuclear PRLr to Coordinate Stat5a-Mediated Transcription. Mol. Endocrinol. 2011, 25:1550-1564.
144. Gomes D.A., Rodrigues M.A., Leite M.F., Gomez M.V., Varnai P., Balla T., Bennett A.M., Nathanson M.H. C-met must translocate to the nucleus to initiate calcium signals. Journal of Biological Chemistry 2008, 283:4344-4351.