Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation

Molecular Oncology

Volumn 7, Issue 6, 2013, Pages 1093-1102

  Kim, Hyeong Ryul ^a   Kim, Woo Sung ^a   Choi, Yun Jung ^a   Choi, Chang Min ^a   Rho, Jin Kyung ^a   Lee, Jae Cheol ^a  

^a University of Ulsan College of Medicine   (South Korea)

Author keywords

ALK; Epithelial mesenchymal transition; Lung cancer; Resistance

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; CRIZOTINIB; PROTEIN; PROTEIN EML4; TRANSFORMING GROWTH FACTOR BETA1; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN;

ARTICLE; CANCER RESISTANCE; CELL INVASION; CELL MIGRATION; CELL VIABILITY; CONTROLLED STUDY; CROSS RESISTANCE; EPITHELIAL MESENCHYMAL TRANSITION; GENE TRANSLOCATION; LONG TERM EXPOSURE; LUNG CANCER; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SECRETION;

ALK; EPITHELIAL-MESENCHYMAL TRANSITION; LUNG CANCER; RESISTANCE;

ANIMALS; CELL MOVEMENT; DRUG RESISTANCE, NEOPLASM; EPITHELIAL-MESENCHYMAL TRANSITION; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LUNG NEOPLASMS; NEOPLASM INVASIVENESS; ONCOGENE PROTEINS, FUSION; PC12 CELLS; PROTEIN KINASE INHIBITORS; PYRAZOLES; PYRIDINES; RATS; TRANSLOCATION, GENETIC;

EID: 84887994377     PISSN: 15747891     EISSN: 18780261     Source Type: Journal    
DOI: 10.1016/j.molonc.2013.08.001     Document Type: Article

References (46)

1. 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.
2. Bergethon K., Shaw A.T., Ou S.H., Katayama R., Lovly C.M., McDonald N.T., Massion P.P., Siwak-Tapp C., Gonzalez A., Fang R., Mark E.J., Batten J.M., Chen H., Wilner K.D., Kwak E.L., Clark J.W., Carbone D.P., Ji H., Engelman J.A., Mino-Kenudson M., Pao W., Iafrate A.J. ROS1 rearrangements define a unique molecular class of lung cancers. J.Clin. Oncol. 2012, 30:863-870.
3. Carmichael J., DeGraff W.G., Gazdar A.F., Minna J.D., Mitchell J.B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987, 47:936-942.
4. Chen Z., Sasaki T., Tan X., Carretero J., Shimamura T., Li D., Xu C., Wang Y., Adelmant G.O., Capelletti M., Lee H.J., Rodig S.J., Borgman C., Park S.I., Kim H.R., Padera R., Marto J.A., Gray N.S., Kung A.L., Shapiro G.I., Janne P.A., Wong K.K. Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 2010, 70:9827-9836.
5. Chiou S.H., Wang M.L., Chou Y.T., Chen C.J., Hong C.F., Hsieh W.J., Chang H.T., Chen Y.S., Lin T.W., Hsu H.S., Wu C.W. Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation. Cancer Res. 2010, 70:10433-10444.
6. Choi Y.L., Soda M., Yamashita Y., Ueno T., Takashima J., Nakajima T., Yatabe Y., Takeuchi K., Hamada T., Haruta H., Ishikawa Y., Kimura H., Mitsudomi T., Tanio Y., Mano H., Group A.L.K.L.C.S. EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N.Engl. J. Med. 2010, 363:1734-1739.
7. Christensen J.G., Zou H.Y., Arango M.E., Li Q., Lee J.H., McDonnell S.R., Yamazaki S., Alton G.R., Mroczkowski B., Los G. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol. Cancer Ther. 2007, 6:3314-3322.
8. Chung J.H., Rho J.K., Xu X., Lee J.S., Yoon H.I., Lee C.T., Choi Y.J., Kim H.R., Kim C.H., Lee J.C. Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs. Lung Cancer 2011, 73:176-182.
9. Dave B., Mittal V., Tan N.M., Chang J.C. Epithelial-mesenchymal transition, cancer stem cells and treatment resistance. Breast Cancer Res. 2012, 14:202.
10. Derynck R., Zhang Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003, 425:577-584.
11. Doebele R.C., Pilling A.B., Aisner D.L., Kutateladze T.G., Le A.T., Weickhardt A.J., Kondo K.L., Linderman D.J., Heasley L.E., Franklin W.A., Varella-Garcia M., Camidge D.R. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin. Cancer Res. 2012, 18:1472-1482.
12. Iwatsuki M., Mimori K., Yokobori T., Ishi H., Beppu T., Nakamori S., Baba H., Mori M. Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 2010, 101:293-299.
13. Kalluri R., Weinberg R.A. The basics of epithelial-mesenchymal transition. J.Clin. Invest 2009, 119:1420-1428.
14. Kasai H., Allen J.T., Mason R.M., Kamimura T., Zhang Z. TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir. Res. 2005, 6:56.
15. Katayama R., Khan T.M., Benes C., Lifshits E., Ebi H., Rivera V.M., Shakespeare W.C., Iafrate A.J., Engelman J.A., Shaw A.T. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc. Natl. Acad. Sci. U S A 2011, 108:7535-7540.
16. Katayama R., Shaw A.T., Khan T.M., Mino-Kenudson M., Solomon B.J., Halmos B., Jessop N.A., Wain J.C., Yeo A.T., Benes C., Drew L., Saeh J.C., Crosby K., Sequist L.V., Iafrate A.J., Engelman J.A. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci. Transl. Med. 2012, 4:120ra117.
17. Kim D.W., Ahn M.J., Shi Y.K., De Pas T.M., Yang P.C., Riely G.J., Crino L., Evans T.L., Liu X.Q., Han J.Y., Salgia R., Moro-Sibilot D., Ou S.H.I., Gettinger S.N., Wu Y.L., Lanzalone S., Polli A., Iyer S., Shaw A.T. Results of a global phase II study with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC). J.Clin. Oncol. 2012, 30.
18. Kwak E.L., Bang Y.J., Camidge D.R., Shaw A.T., Solomon B., Maki R.G., Ou S.H., Dezube B.J., Janne P.A., Costa D.B., Varella-Garcia M., Kim W.H., Lynch T.J., Fidias P., Stubbs H., Engelman J.A., Sequist L.V., Tan W., Gandhi L., Mino-Kenudson M., Wei G.C., Shreeve S.M., Ratain M.J., Settleman J., Christensen J.G., Haber D.A., Wilner K., Salgia R., Shapiro G.I., Clark J.W., Iafrate A.J. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N.Engl. J. Med. 2010, 363:1693-1703.
19. Lee J.M., Dedhar S., Kalluri R., Thompson E.W. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J.Cell Biol. 2006, 172:973-981.
20. Massague J., Blain S.W., Lo R.S. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 2000, 103:295-309.
21. Massague J., Chen Y.G. Controlling TGF-beta signaling. Genes Dev. 2000, 14:627-644.
22. Morris S.W., Kirstein M.N., Valentine M.B., Dittmer K.G., Shapiro D.N., Saltman D.L., Look A.T. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994, 263:1281-1284.
23. O'Hare T., Eide C.A., Deininger M.W. Bcr-Abl kinase domain mutations and the unsettled problem of Bcr-AblT315I: looking into the future of controlling drug resistance in chronic myeloid leukemia. Clin. Lymphoma. Myeloma 2007, 7(Suppl. 3):S120-S130.
24. Rho J.K., Choi Y.J., Lee J.K., Ryoo B.Y., Na I.I., Yang S.H., Kim C.H., Lee J.C. Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer 2009, 63:219-226.
25. Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.L., Polakiewicz R.D., Rush J., Comb M.J. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007, 131:1190-1203.
26. Sang J., Acquaviva J., Friedland J.C., Smith D.L., Sequeira M., Zhang C., Jiang Q., Xue L., Lovly C.M., Jimenez J.P., Shaw A.T., Doebele R.C., He S., Bates R.C., Camidge D.R., Morris S.W., El-Hariry I., Proia D.A. Targeted inhibition of the molecular chaperone Hsp90 overcomes ALK inhibitor resistance in non-small cell lung cancer. Cancer Discov. 2013, 3:430-443.
27. Sasaki T., Koivunen J., Ogino A., Yanagita M., Nikiforow S., Zheng W., Lathan C., Marcoux J.P., Du J., Okuda K., Capelletti M., Shimamura T., Ercan D., Stumpfova M., Xiao Y., Weremowicz S., Butaney M., Heon S., Wilner K., Christensen J.G., Eck M.J., Wong K.K., Lindeman N., Gray N.S., Rodig S.J., Janne P.A. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011, 71:6051-6060.
28. Savagner P. The epithelial-mesenchymal transition (EMT) phenomenon. Ann. Oncol. 2010, 21(Suppl. 7):vii89-vii92.
29. Sawai A., Chandarlapaty S., Greulich H., Gonen M., Ye Q., Arteaga C.L., Sellers W., Rosen N., Solit D.B. Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors to paclitaxel. Cancer Res. 2008, 68:589-596.
30. Scheel C., Weinberg R.A. Cancer stem cells and epithelial-mesenchymal transition: concepts and molecular links. Semin. Cancer Biol. 2012, 22:396-403.
31. Sequist L.V., Waltman B.A., Dias-Santagata D., Digumarthy S., Turke A.B., Fidias P., Bergethon K., Shaw A.T., Gettinger S., Cosper A.K., Akhavanfard S., Heist R.S., Temel J., Christensen J.G., Wain J.C., Lynch T.J., Vernovsky K., Mark E.J., Lanuti M., Iafrate A.J., Mino-Kenudson M., Engelman J.A. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 2011, 3:75ra26.
32. Shaw A.T., Yeap B.Y., Mino-Kenudson M., Digumarthy S.R., Costa D.B., Heist R.S., Solomon B., Stubbs H., Admane S., McDermott U., Settleman J., Kobayashi S., Mark E.J., Rodig S.J., Chirieac L.R., Kwak E.L., Lynch T.J., Iafrate A.J. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J.Clin. Oncol. 2009, 27:4247-4253.
33. Shimamura T., Li D., Ji H., Haringsma H.J., Liniker E., Borgman C.L., Lowell A.M., Minami Y., McNamara K., Perera S.A., Zaghlul S., Thomas R.K., Greulich H., Kobayashi S., Chirieac L.R., Padera R.F., Kubo S., Takahashi M., Tenen D.G., Meyerson M., Wong K.K., Shapiro G.I. Hsp90 inhibition suppresses mutant EGFR-T790M signaling and overcomes kinase inhibitor resistance. Cancer Res. 2008, 68:5827-5838.
34. Singh A., Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010, 29:4741-4751.
35. Soda M., Choi Y.L., Enomoto M., Takada S., Yamashita Y., Ishikawa S., Fujiwara S., Watanabe H., Kurashina K., Hatanaka H., Bando M., Ohno S., Ishikawa Y., Aburatani H., Niki T., Sohara Y., Sugiyama Y., Mano H. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007, 448:561-566.
36. Soda M., Takada S., Takeuchi K., Choi Y.L., Enomoto M., Ueno T., Haruta H., Hamada T., Yamashita Y., Ishikawa Y., Sugiyama Y., Mano H. A mouse model for EML4-ALK-positive lung cancer. Proc. Natl. Acad. Sci. U S A 2008, 105:19893-19897.
37. Solomon B., Varella-Garcia M., Camidge D.R. ALK gene rearrangements: a new therapeutic target in a molecularly defined subset of non-small cell lung cancer. J.Clin. Oncol. 2009, 4:1450-1454.
38. Takeuchi K., Choi Y.L., Togashi Y., Soda M., Hatano S., Inamura K., Takada S., Ueno T., Yamashita Y., Satoh Y., Okumura S., Nakagawa K., Ishikawa Y., Mano H. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin. Cancer Res. 2009, 15:3143-3149.
39. Thomson S., Buck E., Petti F., Griffin G., Brown E., Ramnarine N., Iwata K.K., Gibson N., Haley J.D. Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res. 2005, 65:9455-9462.
40. Togashi Y., Soda M., Sakata S., Sugawara E., Hatano S., Asaka R., Nakajima T., Mano H., Takeuchi K. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One 2012, 7:e31323.
41. Vikis H., Sato M., James M., Wang D., Wang Y., Wang M., Jia D., Liu Y., Bailey-Wilson J.E., Amos C.I., Pinney S.M., Petersen G.M., de Andrade M., Yang P., Wiest J.S., Fain P.R., Schwartz A.G., Gazdar A., Gaba C., Rothschild H., Mandal D., Kupert E., Seminara D., Viswanathan A., Govindan R., Minna J., Anderson M.W., You M. EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity. Cancer Res. 2007, 67:4665-4670.
42. Wong D.W., Leung E.L., So K.K., Tam I.Y., Sihoe A.D., Cheng L.C., Ho K.K., Au J.S., Chung L.P., Pik Wong M., University of Hong Kong Lung Cancer Study, G. TheEML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009, 115:1723-1733.
43. Wrighton K.H., Lin X., Feng X.H. Critical regulation of TGFbeta signaling by Hsp90. Proc. Natl. Acad. Sci. United State. America 2008, 105:9244-9249.
44. Yauch R.L., Januario T., Eberhard D.A., Cavet G., Zhu W., Fu L., Pham T.Q., Soriano R., Stinson J., Seshagiri S., Modrusan Z., Lin C.Y., O'Neill V., Amler L.C. Epithelial versus mesenchymal phenotype determines invitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin. Cancer Res. 2005, 11:8686-8698.
45. Zavadil J., Bottinger E.P. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 2005, 24:5764-5774.
46. Zhang Z., Lee J.C., Lin L., Olivas V., Au V., LaFramboise T., Abdel-Rahman M., Wang X., Levine A.D., Rho J.K., Choi Y.J., Choi C.M., Kim S.W., Jang S.J., Park Y.S., Kim W.S., Lee D.H., Lee J.S., Miller V.A., Arcila M., Ladanyi M., Moonsamy P., Sawyers C., Boggon T.J., Ma P.C., Costa C., Taron M., Rosell R., Halmos B., Bivona T.G. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat. Genet. 2012, 44:852-860.