Constitutive asymmetric dimerization drives oncogenic activation of epidermal growth factor receptor carboxyl-terminal deletion mutants

Oncotarget

Volumn 6, Issue 11, 2015, Pages 8839-8850

  Park, Angela K J ^a,b   Francis, Joshua M ^c   Park, Woong Yang ^a,b   Park, Joon Oh ^d   Cho, Jeonghee ^a,b  

^a Samsung Medical Center   (South Korea)

^b Sungkyunkwan University   (South Korea)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^d Sungkyunkwan University School of Medicine   (South Korea)

Author keywords

Asymmetric dimerization; EGFR C terminal domain deletion; EGFR targeted therapy; Epidermal growth factor receptor

Indexed keywords

AFATINIB; CETUXIMAB; DACOMITINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; LIGAND; ANTINEOPLASTIC AGENT; EGFR PROTEIN, HUMAN; HYBRID PROTEIN; PROTEIN KINASE INHIBITOR; TUMOR PROTEIN;

ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CARCINOGENESIS; CELL TRANSFORMATION; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; DELETION MUTANT; DIMERIZATION; GENE DELETION; GENE MUTATION; GENETIC MARKER; GLIOBLASTOMA; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; PATHOGENESIS; PROTEIN DOMAIN; TREATMENT OUTCOME; 3T3 CELL LINE; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; ENZYME ACTIVATION; EXON; GENETICS; HUMAN; IC50; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; NEOPLASMS, EXPERIMENTAL; NUDE MOUSE; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN PROCESSING; PROTEIN TERTIARY STRUCTURE; PROTO ONCOGENE; RANDOMIZATION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; TUMOR STEM CELL ASSAY; XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; ENZYME ACTIVATION; EXONS; GENES, ERBB-1; HETEROGRAFTS; HUMANS; INHIBITORY CONCENTRATION 50; MICE; MICE, NUDE; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM PROTEINS; NEOPLASMS, EXPERIMENTAL; NIH 3T3 CELLS; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STRUCTURE, TERTIARY; RANDOM ALLOCATION; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECOMBINANT FUSION PROTEINS; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR STEM CELL ASSAY;

EID: 84928716950     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.3559     Document Type: Article

References (52)

1. Hynes NE and MacDonald G. ErbB receptors and signaling pathways in cancer. Current opinion in cell biology. 2009; 21(2):177-184.
2. Pines G, Kostler WJ and Yarden Y. Oncogenic mutant forms of EGFR: lessons in signal transduction and targets for cancer therapy. FEBS letters. 2010; 584(12):2699-2706.
3. Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008; 455(7216):1061-1068.
4. Chan SK, Gullick WJ and Hill ME. Mutations of the epidermal growth factor receptor in non-small cell lung cancer--search and destroy. European journal of cancer. 2006; 42(1):17-23.
5. da Cunha Santos G, Shepherd FA and Tsao MS. EGFR mutations and lung cancer. Annual review of pathology. 2011; 6:49-69.
6. Sharma SV, Bell DW, Settleman J and Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nature reviews Cancer. 2007; 7(3):169-181.
7. Robinson KW and Sandler AB. EGFR tyrosine kinase inhibitors: difference in efficacy and resistance. Current oncology reports. 2013; 15(4):396-404.
8. Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. The New England journal of medicine. 2010; 362(25):2380-2388.
9. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304(5676):1497-1500.
10. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, Mardis E, Kupfer D, Wilson R, Kris M and Varmus H. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101(36):13306-13311.
11. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J and Haber DA. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. The New England journal of medicine. 2004; 350(21):2129-2139.
12. Lee JC, Vivanco I, Beroukhim R, Huang JH, Feng WL, DeBiasi RM, Yoshimoto K, King JC, Nghiemphu P, Yuza Y, Xu Q, Greulich H, Thomas RK, Paez JG, Peck TC, Linhart DJ, et al. Epidermal growth factor receptor activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS medicine. 2006; 3(12):e485.
13. Schwechheimer K, Huang S and Cavenee WK. EGFR gene amplification--rearrangement in human glioblastomas. International journal of cancer Journal international du cancer. 1995; 62(2):145-148.
14. Frederick L, Wang XY, Eley G and James CD. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer research. 2000; 60(5):1383-1387.
15. Ekstrand AJ, Sugawa N, James CD and Collins VP. 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. Proceedings of the National Academy of Sciences of the United States of America. 1992; 89(10):4309-4313.
16. Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, et al. The somatic genomic landscape of glioblastoma. Cell. 2013; 155(2):462-477.
17. Vivanco I, Robins HI, Rohle D, Campos C, Grommes C, Nghiemphu PL, Kubek S, Oldrini B, Chheda MG, Yannuzzi N, Tao H, Zhu S, Iwanami A, Kuga D, Dang J, Pedraza A, et al. Differential sensitivity of glioma-versus lung cancerspecific EGFR mutations to EGFR kinase inhibitors. Cancer discovery. 2012; 2(5):458-471.
18. Rich JN, Reardon DA, Peery T, Dowell JM, Quinn JA, Penne KL, Wikstrand CJ, Van Duyn LB, Dancey JE, McLendon RE, Kao JC, Stenzel TT, Ahmed Rasheed BK, Tourt-Uhlig SE, Herndon JE, 2nd, Vredenburgh JJ, et al. Phase II trial of gefitinib in recurrent glioblastoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004; 22(1):133-142.
19. Cho J, Pastorino S, Zeng Q, Xu X, Johnson W, Vandenberg S, Verhaak R, Cherniack AD, Watanabe H, Dutt A, Kwon J, Chao YS, Onofrio RC, Chiang D, Yuza Y, Kesari S, et al. Glioblastoma-derived epidermal growth factor receptor carboxyl-terminal deletion mutants are transforming and are sensitive to EGFR-directed therapies. Cancer research. 2011; 71(24):7587-7596.
20. Furgason JM, Li W, Milholland B, Cross E, Li Y, McPherson CM, Warnick RE, Rixe O, Stambrook PJ, Vijg J and Bahassi el M. Whole genome sequencing of glioblastoma multiforme identifies multiple structural variations involved in EGFR activation. Mutagenesis. 2014; 29(5):341-350.
21. Imielinski M, Berger AH, Hammerman PS, Hernandez B, Pugh TJ, Hodis E, Cho J, Suh J, Capelletti M, Sivachenko A, Sougnez C, Auclair D, Lawrence MS, Stojanov P, Cibulskis K, Choi K, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012; 150(6):1107-1120.
22. Pines G, Huang PH, Zwang Y, White FM and Yarden Y. EGFRvIV: a previously uncharacterized oncogenic mutant reveals a kinase autoinhibitory mechanism. Oncogene. 2010; 29(43):5850-5860.
23. Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P and Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer cell. 2005; 7(4):301-311.
24. Yu HA and Pao W. Targeted therapies: Afatinib--new therapy option for EGFR-mutant lung cancer. Nature reviews Clinical oncology. 2013; 10(10):551-552.
25. Engelman JA, Zejnullahu K, Gale CM, Lifshits E, Gonzales AJ, Shimamura T, Zhao F, Vincent PW, Naumov GN, Bradner JE, Althaus IW, Gandhi L, Shapiro GI, Nelson JM, Heymach JV, Meyerson M, et al. PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer research. 2007; 67(24):11924-11932.
26. Janne PA, Ou SH, Kim DW, Oxnard GR, Martins R, Kris MG, Dunphy F, Nishio M, O'Connell J, Paweletz C, Taylor I, Zhang H, Goldberg Z and Mok T. Dacomitinib as firstline treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: a multicentre, open-label, phase 2 trial. The Lancet Oncology. 2014; 15(13):1433-1441.
27. Jura N, Endres NF, Engel K, Deindl S, Das R, Lamers MH, Wemmer DE, Zhang X and Kuriyan J. Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment. Cell. 2009; 137(7):1293-1307.
28. Zhang X, Gureasko J, Shen K, Cole PA and Kuriyan J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell. 2006; 125(6):1137-1149.
29. Wang Z, Longo PA, Tarrant MK, Kim K, Head S, Leahy DJ and Cole PA. Mechanistic insights into the activation of oncogenic forms of EGF receptor. Nat Struct Mol Biol. 2011; 18(12):1388-1393.
30. Cho J, Chen L, Sangji N, Okabe T, Yonesaka K, Francis JM, Flavin RJ, Johnson W, Kwon J, Yu S, Greulich H, Johnson BE, Eck MJ, Janne PA, Wong KK and Meyerson M. Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization. Cancer research. 2013; 73(22):6770-6779.
31. Cho J, Bass AJ, Lawrence MS, Cibulskis K, Cho A, Lee SN, Yamauchi M, Wagle N, Pochanard P, Kim N, Park AK, Won J, Hur HS, Greulich H, Ogino S, Sougnez C, et al. Colon cancer-derived oncogenic EGFR G724S mutant identified by whole genome sequence analysis is dependent on asymmetric dimerization and sensitive to cetuximab. Molecular cancer. 2014; 13:141.
32. Gotoh N, Tojo A, Muroya K, Hashimoto Y, Hattori S, Nakamura S, Takenawa T, Yazaki Y and Shibuya M. Epidermal growth factor-receptor mutant lacking the autophosphorylation sites induces phosphorylation of Shc protein and Shc-Grb2/ASH association and retains mitogenic activity. Proceedings of the National Academy of Sciences of the United States of America. 1994; 91(1):167-171.
33. Maegawa M, Arao T, Yokote H, Matsumoto K, Kudo K, Tanaka K, Kaneda H, Fujita Y, Ito F and Nishio K. Epidermal growth factor receptor lacking C-terminal autophosphorylation sites retains signal transduction and high sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor. Cancer science. 2009; 100(3):552-557.
34. Jiang J, Greulich H, Janne PA, Sellers WR, Meyerson M and Griffin JD. Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression. Cancer research. 2005; 65(19):8968-8974.
35. Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F, Rettig WJ, Meyerson M, Solca F, Greulich H and Wong KK. BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008; 27(34):4702-4711.
36. Takagi S, Banno H, Hayashi A, Tamura T, Ishikawa T and Ohta Y. HER2 and HER3 cooperatively regulate cancer cell growth and determine sensitivity to the novel investigational EGFR/HER2 kinase inhibitor TAK-285. Oncoscience. 2014; 1(3):196-204.
37. Wells A, Welsh JB, Lazar CS, Wiley HS, Gill GN and Rosenfeld MG. Ligand-induced transformation by a noninternalizing epidermal growth factor receptor. Science. 1990; 247(4945):962-964.
38. Decker SJ, Alexander C and Habib T. Epidermal growth factor (EGF)-stimulated tyrosine phosphorylation and EGF receptor degradation in cells expressing EGF receptors truncated at residue 973. The Journal of biological chemistry. 1992; 267(2):1104-1108.
39. Hampton KK and Craven RJ. Pathways driving the endocytosis of mutant and wild-type EGFR in cancer. Oncoscience. 2014; 1(8):504-512.
40. Grovdal LM, Stang E, Sorkin A and Madshus IH. Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation. Experimental cell research. 2004; 300(2):388-395.
41. Wang Q, Zhu F and Wang Z. Identification of EGF receptor C-terminal sequences 1005-1017 and di-leucine motif 1010LL1011 as essential in EGF receptor endocytosis. Experimental cell research. 2007; 313(15):3349-3363.
42. Masui H, Wells A, Lazar CS, Rosenfeld MG and Gill GN. Enhanced tumorigenesis of NR6 cells which express nondown-regulating epidermal growth factor receptors. Cancer research. 1991; 51(22):6170-6175.
43. Shan Y, Eastwood MP, Zhang X, Kim ET, Arkhipov A, Dror RO, Jumper J, Kuriyan J and Shaw DE. Oncogenic mutations counteract intrinsic disorder in the EGFR kinase and promote receptor dimerization. Cell. 2012; 149(4):860-870.
44. Lemmon MA, Schlessinger J and Ferguson KM. The EGFR family: not so prototypical receptor tyrosine kinases. Cold Spring Harbor perspectives in biology. 2014; 6(4):a020768.
45. Gajiwala KS. EGFR: tale of the C-terminal tail. Protein science : a publication of the Protein Society. 2013; 22(7):995-999.
46. Landau M, Fleishman SJ and Ben-Tal N. A putative mechanism for downregulation of the catalytic activity of the EGF receptor via direct contact between its kinase and C-terminal domains. Structure. 2004; 12(12):2265-2275.
47. Falchook GS, Naing A, Wheler JJ, Tsimberidou AM, Zinner R, Hong DS, Fu S, Piha-Paul SA, Janku F, Hess KR, Bastida C and Kurzrock R. Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal cancer. Oncoscience. 2014; 1(8):540-549.
48. Schlessinger J. Receptor tyrosine kinases: legacy of the first two decades. Cold Spring Harbor perspectives in biology. 2014; 6(3).
49. Lemmon MA and Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-1134.
50. Kim YN, Wiepz GJ, Guadarrama AG and Bertics PJ. Epidermal growth factor-stimulated tyrosine phosphorylation of caveolin-1. Enhanced caveolin-1 tyrosine phosphorylation following aberrant epidermal growth factor receptor status. The Journal of biological chemistry. 2000; 275(11):7481-7491.
51. Rothenberg SM, Engelman JA, Le S, Riese DJ, 2nd, Haber DA and Settleman J. Modeling oncogene addiction using RNA interference. Proc Natl Acad Sci U S A. 2008; 105(34):12480-12484.
52. Greulich H, Chen TH, Feng W, Janne PA, Alvarez JV, Zappaterra M, Bulmer SE, Frank DA, Hahn WC, Sellers WR and Meyerson M. Oncogenic transformation by inhibitor-sensitive and-resistant EGFR mutants. PLoS medicine. 2005; 2(11):e313.