Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer

Oncogene

Volumn 32, Issue 29, 2013, Pages 3420-3431

  Linger, R M A ^a   Cohen, R A ^a   Cummings, C T ^a   Sather, S ^a   Migdall Wilson, J ^a   Middleton, D H G ^a   Lu, X ^a   Baron A E ^a   Franklin, W A ^b   Merrick, D T ^b,c   Jedlicka, P ^b   Deryckere, D ^a   Heasley, L E ^a   Graham, D K ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Chemosensitivity; MerTK; Receptor tyrosine kinase; Signal transduction; Targeted therapy; Xenograft

Indexed keywords

AX1 RECEPTOR TYROSINE KINASE; CARBOPLATIN; CISPLATIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; DOXORUBICIN; ETOPOSIDE; MESSENGER RNA; METHANOL EXTRACTION RESIDUE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; SHORT HAIRPIN RNA; SURVIVIN; TUBULIN; UNCLASSIFIED DRUG;

ADULT; AGED; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; CANCER INHIBITION; CHEMOSENSITIVITY; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; FEMALE; HUMAN; HUMAN TISSUE; IMMUNOPRECIPITATION; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TUMOR XENOGRAFT;

ANIMALS; APOPTOSIS; BLOTTING, WESTERN; CARCINOMA, NON-SMALL-CELL LUNG; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; FEMALE; GENE KNOCKDOWN TECHNIQUES; HUMANS; IMMUNOPRECIPITATION; LUNG NEOPLASMS; MALE; MICE; MIDDLE AGED; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TISSUE ARRAY ANALYSIS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

MUS MUSCULUS;

EID: 84880922644     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2012.355     Document Type: Article

References (65)

1. Society AC. Cancer Facts & Figures 2012. American Cancer Society: Atlanta, 2012.
2. SEER Cancer Statistics Review, 1975-2008 [database on the Internet] National Cancer Institute, 2011 [cited 1/25/2012]. Available from: http://seer.cancer.gov/ csr/1975-2008/.
3. Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 2011; 12: 1004-1012.
4. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957.
5. Paik PK, Arcila ME, Fara M, Sima CS, Miller VA, Kris MG et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol 2011; 29: 2046-2051.
6. Brose MS, Volpe P, Feldman M, Kumar M, Rishi I, Gerrero R et al. BRAF and RAS mutations in human lung cancer and melanoma. Cancer Res 2002; 62: 6997-7000. (Pubitemid 35424092)
7. Yamamoto H, Shigematsu H, Nomura M, Lockwood WW, Sato M, Okumura N et al. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 2008; 68: 6913-6921.
8. Shigematsu H, Takahashi T, Nomura M, Majmudar K, Suzuki M, Lee H et al. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas. Cancer Res 2005; 65: 1642-1646. (Pubitemid 40478587)
9. Engelman JA, Zejnullahu K, Gale CM, Lifshits E, Gonzales AJ, Shimamura T 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 Res 2007; 67: 11924-11932.
10. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008; 14: 1351-1356.
11. Pratilas CA, Hanrahan AJ, Halilovic E, Persaud Y, Soh J, Chitale D et al. Genetic predictors of MEK dependence in non-small cell lung cancer. Cancer Res 2008; 68: 9375-9383.
12. Sunaga N, Shames DS, Girard L, Peyton M, Larsen JE, Imai H et al. Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy. Mol Cancer Ther 2011; 10: 336-346.
13. Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L et al. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther 2011; 10: 2426-2436.
14. Janku F, Garrido-Laguna I, Petruzelka LB, Stewart DJ, Kurzrock R. Novel therapeutic targets in non-small cell lung cancer. J Thorac Oncol 2011; 6: 1601-1612.
15. Linger RMA, Keating AK, Earp HS, Graham DK. TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res 2008; 100: 35-83. (Pubitemid 351932179)
16. Brandao L, Migdall-Wilson J, Eisenman K, Graham DK. TAM receptors in leukemia: expression, signaling, and therapeutic implications. Critical reviews in oncogenesis 2011; 16: 47-63.
17. Linger RMA, Keating AK, Earp HS, Graham DK. Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors. Expert Opin Ther Targets 2010; 14: 1073-1090.
18. Li Y, Ye X, Tan C, Hongo JA, Zha J, Liu J et al. Axl as a potential therapeutic target in cancer: role of Axl in tumor growth, metastasis and angiogenesis. Oncogene 2009; 28: 3442-3455.
19. Ye X, Li Y, Stawicki S, Couto S, Eastham-Anderson J, Kallop D et al. An anti-Axl monoclonal antibody attenuates xenograft tumor growth and enhances the effect of multiple anticancer therapies. Oncogene 2010; 29: 5254-5264.
20. Shieh YS, Lai CY, Kao YR, Shiah SG, Chu YW, Lee HS et al. Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia 2005; 7: 1058-1064.
21. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007; 131: 1190-1203. (Pubitemid 350235027)
22. Bremnes RM, Veve R, Gabrielson E, Hirsch FR, Baron A, Bemis L et al. Highthroughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol 2002; 20: 2417-2428. (Pubitemid 34525727)
23. Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev 2004; 68: 320-344. (Pubitemid 38756868)
24. Aggarwal S, Kim SW, Ryu SH, Chung WC, Koo JS. Growth suppression of lung cancer cells by targeting cyclic AMP response element-binding protein. Cancer Res 2008; 68: 981-988. (Pubitemid 351272215)
25. Reeve JG, Xiong J, Morgan J, Bleehen NM. Expression of apoptosis-regulatory genes in lung tumour cell lines: relationship to p53 expression and relevance to acquired drug resistance. Br J Cancer 1996; 73: 1193-1200. (Pubitemid 26162332)
26. Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE et al. Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem 2000; 275: 10761-10766. (Pubitemid 30212704)
27. Zhang LQ, Wang J, Jiang F, Xu L, Liu FY, Yin R. Prognostic value of survivin in patients with non-small cell lung carcinoma: a systematic review with meta-analysis. PLoS One 2012; 7: e34100.
28. Arriola EL, Rodriguez-Lopez AM, Hickman JA, Chresta CM. Bcl-2 overexpression results in reciprocal downregulation of Bcl-X(L) and sensitizes human testicular germ cell tumours to chemotherapy-induced apoptosis. Oncogene 1999; 18: 1457-1464. (Pubitemid 29103633)
29. Lin B, Kolluri SK, Lin F, Liu W, Han YH, Cao X et al. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell 2004; 116: 527-540. (Pubitemid 38264430)
30. Oliver L, Hue E, Rossignol J, Bougras G, Hulin P, Naveilhan P et al. Distinct roles of Bcl-2 and Bcl-Xl in the apoptosis of human bone marrow mesenchymal stem cells during differentiation. PLoS One 2011; 6: e19820.
31. Shinoura N, Yoshida Y, Nishimura M, Muramatsu Y, Asai A, Kirino T et al. Expression level of Bcl-2 determines anti- or proapoptotic function. Cancer Res 1999; 59: 4119-4128. (Pubitemid 29393587)
32. Grosso S, Puissant A, Dufies M, Colosetti P, Jacquel A, Lebrigand K et al. Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors. Mol Cancer Ther 2009; 8: 1924-1933.
33. Liu L, Greger J, Shi H, Liu Y, Greshock J, Annan R et al. Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. Cancer Res 2009; 69: 6871-6878.
34. Mahadevan D, Cooke L, Riley C, Swart R, Simons B, Della Croce K et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene 2007; 26: 3909-3919. (Pubitemid 46884299)
35. Holland SJ, Pan A, Franci C, Hu Y, Chang B, Li W et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res 2010; 70: 1544-1554.
36. Hong CC, Lay JD, Huang JS, Cheng AL, Tang JL, Lin MT et al. Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia. Cancer Lett 2008; 268: 314-324.
37. Macleod K, Mullen P, Sewell J, Rabiasz G, Lawrie S, Miller E et al. Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. Cancer Res 2005; 65: 6789-6800. (Pubitemid 41060717)
38. Keating AK, Kim GK, Jones AE, Donson AM, Ware K, Mulcahy JM et al. Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma leads to increased apoptosis and improved chemosensitivity. Mol Cancer Ther 2010; 9: 1298-1307.
39. Keating AK, Salzberg DB, Sather S, Liang X, Nickoloff S, Anwar A et al. Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase. Oncogene 2006; 25: 6092-6100. (Pubitemid 44562407)
40. Wimmel A, Glitz D, Kraus A, Roeder J, Schuermann M. Axl receptor tyrosine kinase expression in human lung cancer cell lines correlates with cellular adhesion. Eur J Cancer 2001; 37: 2264-2274. (Pubitemid 33001299)
41. Balogh I, Hafizi S, Stenhoff J, Hansson K, Dahlback B. Analysis of Gas6 in human platelets and plasma. Arterioscler Thromb Vasc Biol 2005; 25: 1280-1286. (Pubitemid 40776622)
42. Gustafsson A, Martuszewska D, Johansson M, Ekman C, Hafizi S, Ljungberg B et al. Differential expression of Axl and Gas6 in renal cell carcinoma reflecting tumor advancement and survival. Clin Cancer Res 2009; 15: 4742-4749.
43. Jansen FH, van Rijswijk A, Teubel W, van Weerden WM, Reneman S, van den Bemd GJ et al. Profiling of antibody production against xenograft-released proteins by protein microarrays discovers prostate cancer markers. J Proteome Res 2012; 11: 728-735.
44. Wu J, Ekman C, Jonsen A, Sturfelt G, Bengtsson AA, Gottsater A et al. Increased plasma levels of the soluble Mer tyrosine kinase receptor in systemic lupus erythematosus relate to disease activity and nephritis. Arthr Res Ther 2011; 13: R62.
45. Ekman C, Jonsen A, Sturfelt G, Bengtsson AA, Dahlback B. Plasma concentrations of Gas6 and sAxl correlate with disease activity in systemic lupus erythematosus. Rheumatology 2011; 50: 1064-1069.
46. Shankar SL, O'Guin K, Kim M, Varnum B, Lemke G, Brosnan CF et al. Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. J Neurosci 2006; 26: 5638-5648. (Pubitemid 44315255)
47. Allen MP, Linseman DA, Udo H, Xu M, Schaack JB, Varnum B et al. Novel mechanism for gonadotropin-releasing hormone neuronal migration involving Gas6/Ark signaling to p38 mitogen-activated protein kinase. Mol Cell Biol 2002; 22: 599-613. (Pubitemid 34027504)
48. Allen MP, Xu M, Linseman DA, Pawlowski JE, Bokoch GM, Heidenreich KA et al. Adhesion-related kinase repression of gonadotropin-releasing hormone gene expression requires Rac activation of the extracellular signal-regulated kinase pathway. J Biol Chem 2002; 277: 38133-38140. (Pubitemid 35154666)
49. Guttridge KL, Luft JC, Dawson TL, Kozlowska E, Mahajan NP, Varnum B et al. Mer receptor tyrosine kinase signaling: prevention of apoptosis and alteration of cytoskeletal architecture without stimulation or proliferation. J Biol Chem 2002; 277: 24057-24066. (Pubitemid 34951918)
50. Mudduluru G, Leupold JH, Stroebel P, Allgayer H. PMA up-regulates the transcription of Axl by AP-1 transcription factor binding to TRE sequences via the MAPK cascade in leukaemia cells. Biol Cell 2011; 103: 21-33.
51. Demarchi F, Verardo R, Varnum B, Brancolini C, Schneider C. Gas6 antiapoptotic signaling requires NF-kappa B activation. J Biol Chem 2001; 276: 31738- 31744.
52. Goruppi S, Chiaruttini C, Ruaro ME, Varnum B, Schneider C. Gas6 induces growth, beta-catenin stabilization, and T-cell factor transcriptional activation in contactinhibited C57 mammary cells. Mol Cell Biol 2001; 21: 902-915. (Pubitemid 32104738)
53. Alciato F, Sainaghi PP, Sola D, Castello L, Avanzi GC. TNF-alpha IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages. J Leukoc Biol 2010; 87: 869-875.
54. Han Z, Chatterjee D, Early J, Pantazis P, Hendrickson EA, Wyche JH. Isolation and characterization of an apoptosis-resistant variant of human leukemia HL-60 cells that has switched expression from Bcl-2 to Bcl-xL. Cancer Res 1996; 56: 1621-1628.
55. Vajkoczy P, Knyazev P, Kunkel A, Capelle HH, Behrndt S, von Tengg-Kobligk H et al. Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival. Proc Natl Acad Sci USA 2006; 103: 5799-5804.
56. Zhang YX, Knyazev PG, Cheburkin YV, Sharma K, Knyazev YP, Orfi L et al. AXL is a potential target for therapeutic intervention in breast cancer progression. Cancer Res 2008; 68: 1905-1915. (Pubitemid 351416577)
57. Gjerdrum C, Tiron C, Hoiby T, Stefansson I, Haugen H, Sandal T et al. Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc Natl Acad Sci USA 2010; 107: 1124-1129.
58. Tai KY, Shieh YS, Lee CS, Shiah SG, Wu CW. Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1. Oncogene 2008; 27: 4044-4055.
59. Nielsen-Preiss SM, Allen MP, Xu M, Linseman DA, Pawlowski JE, Bouchard RJ et al. Adhesion-related kinase induction of migration requires phosphatidylinositol-3- kinase and ras stimulation of rac activity in immortalized gonadotropin-releasing hormone neuronal cells. Endocrinology 2007; 148: 2806-2814. (Pubitemid 46984802)
60. Rogers AE, Le JP, Sather S, Pernu BM, Graham DK, Pierce AM et al. Mer receptor tyrosine kinase inhibition impedes glioblastoma multiforme migration and alters cellular morphology. Oncogene 2012; 31: 4171-4181.
61. Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 2001; 411: 207-211. (Pubitemid 32455181)
62. Wu Y, Singh S, Georgescu MM, Birge RB. A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci 2005; 118: 539-553. (Pubitemid 40310121)
63. Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull 1979; 86: 420-428.
64. Ramirez RD, Sheridan S, Girard L, Sato M, Kim Y, Pollack J et al. Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res 2004; 64: 9027-9034. (Pubitemid 39665513)
65. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006; 1: 2315-2319.