Molecular pathways: MERTK signaling in cancer

Clinical Cancer Research

Volumn 19, Issue 19, 2013, Pages 5275-5280

  Cummings, Christopher T ^a   DeRyckere, Deborah ^a   Earp, H Shelton ^b   Graham, Douglas K ^a  

^a University of Colorado Denver and Children s Hospital Colorado   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BMS 777607; COMPOUND 52; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; FOCAL ADHESION KINASE; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; JANUS KINASE; MAMMALIAN TARGET OF RAPAMYCIN; MER RECEPTOR TYROSINE KINASE; MICRORNA 126; MITOGEN ACTIVATED PROTEIN KINASE; MYOSIN LIGHT CHAIN 2; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BCL 2; PROTEIN C FOS; PROTEIN C JUN; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; R 428; RAF PROTEIN; S6 KINASE; SHORT HAIRPIN RNA; STAT PROTEIN; STAT5 PROTEIN; STAT6 PROTEIN; SUNITINIB; UNC 1062; UNC 569; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CARCINOGENESIS; CELL MIGRATION; COLON CANCER; COLONY FORMATION; DRUG BIOAVAILABILITY; DRUG RESISTANCE; DRUG SELECTIVITY; DRUG SENSITIVITY; ENZYME INHIBITION; GLIOBLASTOMA; HUMAN; HYPOPHYSIS ADENOMA; LEUKEMIA; LUNG NON SMALL CELL CANCER; MELANOMA; NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; RHABDOMYOSARCOMA; SIGNAL TRANSDUCTION; STOMACH CANCER;

ANTINEOPLASTIC AGENTS; HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84886384644     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-12-1451     Document Type: Article

References (60)

1. Linger RM, 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.
2. MahajanNP, Whang YE, Mohler JL, Earp HS. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res 2005;65:10514-23.
3. Sather S, Kenyon KD, Lefkowitz JB, Liang X, Varnum BC, Henson PM, et al. A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood 2007;109:1026-33.
4. Angelillo-Scherrer A, Burnier L, Flores N, Savi P, DeMol M, Schaeffer P, et al. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy. J Clin Invest 2005;115:237-46.
5. 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;411:207-11.
6. Camenisch TD, Koller BH, Earp HS, Matsushima GK. A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide- induced endotoxic shock. J Immunol 1999;162: 3498-503.
7. Graham DK, Dawson TL, Mullaney DL, Snodgrass HR, Earp HS. Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ 1994;5:647-57.
8. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002;1:133-43.
9. Graham DK, Salzberg DB, Kurtzberg J, Sather S, Matsushima GK, Keating AK, et al. Ectopic expression of the proto-oncogene Mer in pediatric T-cell acute lymphoblastic leukemia. Clin Cancer Res 2006; 12:2662-9.
10. Brandao LN, Winges A, Christoph S, Sather S, Migdall-Wilson J, Schlegel J, et al. Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia. Blood Cancer J 2013;3:e101.
11. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008;451:147-52.
12. Png KJ, Halberg N, Yoshida M, Tavazoie SF., A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 2011;481:190-4.
13. Watanabe T, Kobunai T, Yamamoto Y, Matsuda K, Ishihara S, Nozawa K, et al. Differential gene expression signatures between colorectal cancers with and without KRAS mutations: crosstalk between the KRAS pathway and other signalling pathways. Eur J Cancer 2011; 47:1946-54.
14. Wu CW, Li AF, Chi CW, Lai CH, Huang CL, Lo SS, et al. Clinical significance of AXL kinase family in gastric cancer. Anticancer Res 2002;22:1071-8.
15. Ling L, Kung HJ. Mitogenic signals and transforming potential of Nyk, a newly identified neural cell adhesion molecule-related receptor tyrosine kinase. Mol Cell Biol 1995;15:6582-92.
16. Keating AK, KimGK, Jones AE, Donson AM, Ware K, Mulcahy JM, et al. Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma cells leads to increased apoptosis and improved chemosensitivity. Mol Cancer Ther 2010;9:1298-307.
17. 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: 4171-81.
18. Wang Y, Moncayo G, Morin P Jr, Xue G, Grzmil M, Lino MM, et al. Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme. Oncogene 2013;32:872-82.
19. Ek S, H?ogerkorp CM, Dictor M, Ehinger M, Borrebaeck CA. Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells. Cancer Res 2002;62:4398-405.
20. Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, et al. Phosphoproteomic screen identifies potential therapeutic targets in melanoma. Mol Cancer Res 2011;9: 801-12.
21. Tworkoski KA, Platt J, Bacchiocchi A, Bosenberg M, Boggon TJ, Stern DF. MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL. Pigment Cell Melanoma Res 2013;26:527-41.
22. Schlegel J, Sambade MJ, Sather S, Moschos SJ, Tan AC, Winges A, et al. MERTK receptor tyrosine kinase is a therapeutic target in melanoma. J Clin Invest. 2013;123:2257-67
23. Linger RM, Cohen RA, Cummings CT, Sather S, Migdall-Wilson J, Middleton DH, et al. Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer. Oncogene. 2012 Aug 13. [Epub ahead of print]
24. Evans CO, Young AN, Brown MR, Brat DJ, Parks JS, Neish AS, et al. Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription- polymerase chain reaction. J Clin Endocrinol Metab 2001;86:3097-107.
25. Wu YM, Robinson DR, Kung HJ. Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells. Cancer Res 2004;64:7311-20.
26. Khan J, Bittner ML, Saal LH, Teichmann U, Azorsa DO, Gooden GC, et al. cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. Proc Natl Acad Sci U S A 1999;96:13264-9.
27. Graham DK, Bowman GW, Dawson TL, Stanford WL, Earp HS, Snodgrass HR. Cloning and developmental expression analysis of the murine c-mer tyrosine kinase. Oncogene 1995;10:2349-59.
28. Jia R, Mayer BJ, Hanafusa T, Hanafusa H. A novel oncogene, v-ryk, encoding a truncated receptor tyrosine kinase is transduced into the RPL30 virus without loss of viral sequences. J Virol 1992;66: 5975-87.
29. Jia R, Hanafusa H. The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine kinase with extracellular Ig/GN-III domains. J Biol Chem 1994;269:1839-44.
30. Lierman E, Van Miegroet H, Beullens E, Cools J. Identification of protein tyrosine kinases with oncogenic potential using a retroviral insertion mutagenesis screen. Haematologica 2009;94:1440-4.
31. Georgescu MM, Kirsch KH, Shishido T, Zong C, Hanafusa H. Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NFkappaB. Mol Cell Biol 1999;19:1171-81.
32. Karin M. Nuclear factor-kappaB in cancer development and progression. Nature 2006;441:431-6.
33. Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 2009;9:537-49.
34. 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;277:24057-66.
35. Chen J, Carey K, Godowski PJ. Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Oncogene 1997;14: 2033-9.
36. Fisher PW, Brigham-Burke M, Wu SJ, Luo J, Carton J, Staquet K, et al. A novel site contributing to growth-arrest-specific gene 6 binding to its receptors as revealed by a human monoclonal antibody. Biochem J 2005;387:727-35.
37. Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, et al. Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem 1996;271:30022-7.
38. Prasad D, Rothlin CV, Burrola P, Burstyn-Cohen T, Lu Q, Garcia de Frutos P, et al. TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci 2006;33:96-108.
39. Manfioletti G, Brancolini C, Avanzi G, Schneider C. The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol 1993; 13:4976-85.
40. Balogh I, Hafizi S, Stenhoff J, Hansson K, Dahlb?ack B. Analysis of Gas6 in human platelets and plasma. Arterioscler Thromb Vasc Biol 2005; 25:1280-6.
41. Uehara H, Shacter E. Auto-oxidation and oligomerization of protein S on the apoptotic cell surface is required for Mer tyrosine kinasemediated phagocytosis of apoptotic cells. J Immunol 2008;180: 2522-30.
42. Caberoy NB, Zhou Y, Li W. Tubby and tubby-like protein 1 are new MerTK ligands for phagocytosis. EMBO J 2010;29:3898-910.
43. Caberoy NB, Alvarado G, Bigcas JL, Li W. Galectin-3 is a new MerTKspecific eat-me signal. J Cell Physiol 2012;227:401-7.
44. Newlaczyl AU, Yu LG. Galectin-3-a jack-of-all-trades in cancer. Cancer Lett 2011;313:123-8.
45. 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;25:6092-100.
46. Bruns HA, Kaplan MH. The role of constitutively active Stat6 in leukemia and lymphoma. Crit Rev Oncol Hematol 2006;57: 245-53.
47. Ferbeyre G, Moriggl R. The role of Stat5 transcription factors as tumor suppressors or oncogenes. Biochim Biophys Act 2011;1815: 104-14.
48. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009;9:798-809.
49. Lee-Sherick AB, Eisenman K, Sather S, McGranahan A, ArmisteadPM, McGary CS, et al. Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia. Oncogene. 2013 Mar 11. [Epub ahead of print].
50. Mahajan NP, Earp HS. An SH2 domain-dependent, phosphotyrosineindependent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J Biol Chem 2003;278:42596-603.
51. Komurov K, Padron D, Cheng T, Roth M, Rosenblatt KP, White MA. Comprehensive mapping of the human kinome to epidermal growth factor receptor signaling. J Biol Chem 2010;285: 21134-42.
52. Migdall-Wilson J, Bates C, Schlegel J, Brandao L, Linger RM, DeRyckere D, et al. Prolonged exposure to a Mer ligand in leukemia: Gas6 favors expression of a partial Mer glycoformand reveals a novel role for Mer in the nucleus. PLoS ONE 2012;7:e31635.
53. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, et al. Patterns of somatic mutation in human cancer genomes. Nature 2007;446:153-8.
54. Hucthagowder V, Meyer R, Mullins C, Nagarajan R, DiPersio JF, Vij R, et al. Resequencing analysis of the candidate tyrosine kinase and RAS pathway gene families in multiple myeloma. Cancer Genet 2012;205: 474-8.
55. Mollard A, Warner SL, Call LT, Wade ML, Bearss JJ, Verma A, et al. Design, synthesis and biological evaluation of a series of novel Axl kinase inhibitors. ACS Med Chem Lett 2011;2:907-12.
56. Schroeder GM, An Y, Cai ZW, Chen XT, Clark C, Cornelius LA, et al. Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1- (4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily. J Med Chem 2009;52:1251-4.
57. 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;70:1544-54.
58. Huang X, Finerty P Jr, Walker JR, Butler-Cole C, Vedadi M, Schapira M, et al. Structural insights into the inhibited states of the Mer receptor tyrosine kinase. J Struct Biol 2009;165:88-96.
59. Liu J, Yang C, Simpson C, Deryckere D, Van Deusen A, Miley MJ, et al. Discovery of novel small molecule Mer kinase inhibitors for the treatment of pediatric acute lymphoblastic leukemia. ACS Med Chem Lett 2012;3:129-34.
60. Liu J, Zhang W, Stashko M, Deryckere D, Cummings CT, Hunter D, et al. UNC1062, a new and potent Mer inhibitor. Eur J Med Chem. 2013 Apr. [Epub ahead of print].