Oncogenic variant RON160 expression in breast cancer and its potential as a therapeutic target by small molecule tyrosine kinase inhibitor

Current Cancer Drug Targets

Volumn 13, Issue 6, 2013, Pages 686-697

  Yao, Hang Ping ^a   Zhuang, Chun Mei ^b   Zhou, Yong Qing ^c   Zeng, Jun Ying ^b   Zhang, Rui Wen ^b   Wang, Ming Hai ^a,b  

^a ZHEJIANG UNIVERSITY   (China)

^b TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^c ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Breast cancer; Kinase; Oncogenic variant; Receptor tyrosine tumor xenograft model; Targeted cancer therapy; Tyrosine kinase inhibitor

Indexed keywords

5 (2, 6 DICHLOROBENZYLSULFONYL) 3 [3, 5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1, 3 DIHYDRO 2H INDOL 2 ONE; 5 (2,6 DICHLOROBENZYLSULFONYL) 3 [3,5 DIMETHYL 4 [2 (1 PYRROLIDINYLMETHYL) 1 PYRROLIDINYLCARBONYL] 1H PYRROL 2 YLMETHYLENE] 1,3 DIHYDRO 2H INDOL 2 ONE; EPIDERMAL GROWTH FACTOR RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN KINASE B; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER INHIBITION; CARCINOGENESIS; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; IMMUNOREACTIVITY; MAJOR CLINICAL STUDY; NONHUMAN; ONCOGENE; PROTEIN PHOSPHORYLATION; RON160 GENE; SCORING SYSTEM; SIGNAL TRANSDUCTION; TISSUE MICROARRAY; TUMOR GROWTH; TUMOR VOLUME; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BREAST NEOPLASMS; CELL LINE, TUMOR; ENZYME INDUCTION; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; GENETIC VARIATION; HUMANS; INDOLES; LYMPHATIC METASTASIS; MAMMARY GLANDS, HUMAN; MICE; MICE, INBRED BALB C; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; PROTEIN KINASE INHIBITORS; RANDOM ALLOCATION; RECEPTOR PROTEIN-TYROSINE KINASES; SULFONES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84881096661     PISSN: 15680096     EISSN: 18735576     Source Type: Journal    
DOI: 10.2174/15680096113139990038     Document Type: Article

References (39)

1. Ronsin, C.; Muscatelli, F.; Mattei, M. G.; Breathnach, R. A novel putative receptor protein tyrosine kinase of the met family. Oncogene 1993, 8, 1195-1202.
2. Trusolino, L.; Comoglio, P. M. Scatter-factor and semaphoring receptors: cell signaling for invasive growth. Nat. Rev. Cancer 2002, 2, 289-300.
3. Thomas, R. M.; Toney, K.; Fenoglio-Preiser, C.; Revelo-Penafiel, M. P.; Hingorani, S. R.; Tuveson, D. A.; Waltz, S. E.; Lowy, A. M. The RON receptor tyrosine kinase mediates oncogenic phenotypes in pancreatic cancer cells and is increasingly expressed during pancreatic cancer progression. Cancer Res. 2007, 67, 6075-6082.
4. Wang, M. H.; Lee, W.; Luo, Y. L.; Weis, M.T.; Yao, H.P. Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumorigenic phenotypes in thyroid cancer cells. J. Pathol. 2007, 213, 402-411.
5. Zhou, Y.Q.; He, C.; Chen, Y. Q.; Wang, D.; Wang, M. H. Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 2003, 22, 186-197.
6. Maggiora, P.; Marchio, S.; Stella, M. C.; Giai, M.; Belfiore, A.; De Bortoli, M.; Di Renzo, M. F.; Costantino, A.; Sismondi, P.; Comoglio, P. M. Overexpression of the RON gene in human breast carcinoma. Oncogene 1998, 16, 2927-2933.
7. Lu, Y.; Yao, H. P.; Wang, M. H. Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Cancer Lett. 2007, 257, 157-164.
8. Ma, Q.; Zhang, K.; Guin, S.; Zhou, Y. Q.; Wang, M. H. Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase. Mol. Cancer 2010, 9, 307-321.
9. Collesi, C.; Santoro, M. M.; Gaudino, G.; Comoglio, P. M. A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Mol. Cell. Biol. 1996, 16, 5518-5526.
10. Eckerich, C.; Schulte, A.; Martens, T.; Zapf, S.; Westphal, M.; Lamszus, K. RON receptor tyrosine kinase in human gliomas: expression, function, and identification of a novel soluble splice variant. J. Neurochem. 2009, 109, 969-980.
11. Liu, X.; Zhao, L.; Derose, Y. S.; Lin, Y. C.; Bieniasz, M.; Eyob, H.; Buys, S. S.; Neumayer, L.; Welm, A. L. Short-Form Ron Promotes Spontaneous Breast Cancer Metastasis through Interaction with Phosphoinositide 3-Kinase. Genes Cancer 2011, 2, 753-762.
12. Wang, M. H.; Kurtz, A. L.; Chen, Y. Q. Identification of a novel splicing product of the RON receptor tyrosine kinase in human colorectal carcinoma cells. Carcinogenesis 2000, 21, 1507-1512.
13. Xu, X. M.; Zhou, Y. Q.; Wang, M. H. Mechanisms of cytoplasmic {beta}-catenin accumulation and its involvement in tumorigenic activities mediated by oncogenic splicing variant of the receptor originated from Nantes tyrosine kinase. J. Bio. Chem. 2005, 280, 25087-25094.
14. Wagh, P. K.; Gray, J. K.; Zinser, G. M.; Vasiliauskas, J.; James, L.; Monga, S. P.; Waltz, S. E.-Catenin is required for Ron receptorinduced mammary tumorigenesis. Oncogene 2011, 30, 3694-3704.
15. Wang, J.; Rajput, A.; Kan, J. L.; Rose, R.; Liu, X. Q.; Kuropatwinski, K.; Hauser, J.; Beko, A.; Dominquez, I.; Sharratt, E. A.; Brattain, L.; Levea, C.; Sun, F. L.; Keane, D. M.; Gibson, N. W.;. Knockdown of Ron kinase inhibits mutant phosphatidylinositol 3-kinase and reduces metastasis in human colon carcinoma. J. Biol. Chem. 2009, 284, 10912-10922.
16. Ma, Q.; Guin, S.; Padhye, S. S.; Zhou, Y. Q.; Zhang, R. W.; Wang, M. H. Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein. Mol. Cancer 2011, 10, 66-80.
17. Zhou, Y. Q.; Luo, Y. L.; Zhou, Z. W.; Yao, H. P.; Wang, M. H. Beta-Arrestin-1-Dependent Activation of Extracellular Signal Regulated Kinases in RON Receptor-Mediated Tumorigenic Activities in Colon Cancer Cells. J. Cancer Mol. 2010, 5, 55-62.
18. Chaudhuri, A.; Xie, M. H.; Yang, B.; Mahapatra, K.; Liu, J.; Marsters, S.; Bodepudi, S.; Ashkenazi, A. Distinct Involvement of the Gab1 and Grb2 Adaptor Proteins in Signal Transduction by the Related Receptor Tyrosine Kinases RON and MET. J. Biol. Chem. 2011, 286, 32762-32774.
19. Thangasamy, A.; Rogge, J.; Ammanamanchi, S. Recepteur d'origine nantais tyrosine kinase is a direct target of hypoxia inducible factor-1alpha-mediated invasion of breast carcinoma cells. J. Biol. Chem. 2009, 284, 14001-14010.
20. Zinser, G. M.; Leonis, M. A.; Toney, K.; Pathrose, P.; Thobe, M.; Kader, S. A.; Peace, B. E.; Beauman, S. R.; Collins, M. H.; Waltz, S. E. Mammary-specific Ron receptor overexpression induces highly metastatic mammary tumors associated with beta-catenin activation. Cancer Res. 2006, 66, 11967-11974.
21. Welm, A. L.; Taylor, C.; Nuyten, D. S.; van de Vijver, M. J.; Hasegawa, B. H.; Bishop, J. M. The macrophagestimulating protein pathway promotes metastasis in a mouse model for breast cancer and predicts poor prognosis in humans. Proc. Natl. Acad. Sci. USA 2007, 104, 7570-7574
22. Lee, W. Y.; Chen, H. H.; Chow, N. H.; Lin, P. W.; Guo, H. R. Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients. Clin. Cancer Res. 2005, 11, 2222-2228.
23. Christensen, J. G.; Schreck, R.; Burrows, J.; Kuruganti, P.; Chan, E.; Le, P.; Chen, J.; Wang, X.; Ruslim, L.; Blake, R.; Lipson, K. E.; Ramphal, J.; Do, S.; Cui, J. J.; Cherrington, J. M.; Mendel, D. B. A selective small molecule inhibitor of c-Met kinase inhibits c-Metdependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res. 2003, 63, 7345-7355.
24. Yao, H. P.; Luo, Y. L.; Feng, L.; Cheng, L. F.; Lu, Y.; Li, W.; Wang, M. Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase. Cancer Biol. Ther. 2006, 5, 1179-1186.
25. Angeloni, D.; Danilkovitch-Miagkova, A.; Ivanov, S. V.; Breathnach, R.; Johnson, B. E.; Leonard, E. J.; Lerman, M. I. Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples. Genes Chromosomes Cancer 2000, 29, 147-156.
26. Guin, S.; Yao, H. P.; Wang, M. H. RON receptor tyrosine kinase as a target for delivery of chemodrugs by antibody directed pathway for cancer cell cytotoxicity. Mol. Pharmaceutics 2010, 7, 386-397.
27. Allred, D. C.; Harvey, J. M.; Berardo, M.; Clark, G. M. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod. Pathol. 1998, 11, 155-168.
28. Potratz, J. C.; Saunders, D. N.; Waim, D. H.; Ng, T. L.; McKinney, S. E.; Carboni, J. M.; Gottardis, M. M.; Triche, T. J.; Jürgens, H.; Pollak, M. N.; Aparicio, S. A.; Sorensen, P. H. Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas. Cancer Res. 2010, 70, 8770-8781.
29. Yao, H. P.; Zhou, Y. Q.; Ma, Q.; Guin, S.; Padhye, S. S.; Zhang, R. W.; Wang, M. H. The monoclonal antibody Zt/f2 targeting RON receptor tyrosine kinase as potential therapeutics against tumor growthmediated by colon cancer cells. Mol. Cancer 2011, 10, 82-94.
30. Ren, X.; Daa, T., Yada, N., Kashima, K., Fujitomi, Y., Yokoyama, S. Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma. APMIS 2012, 120, 3558-3567.
31. Langlois, A. J.; Holder, W. D. Jr.; Iglehart, J. D.; Nelson-Rees, W. A.; Wells, S. A. Jr.; Bolognesi, D. P. Morphological and biochemical properties of a new human breast cancer cell line. Cancer Res. 1979, 39, 2604-2613.
32. Lefave, C. V.; Squatrito, M.; Vorlova, S.; Rocco, G. L.; Brennan, C. W.; Holland, E. C.; Pan, Y. X.; Cartegni, L. Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas. EMBO J. 2011, 30, 4084-4097.
33. Ghigna, C.; Giordano, S.; Shen, H.; Benvenuto, F.; Castiglioni, F.; Comoglio, P. M.; Green, M. R.; Riva, S.; Biamonti, G. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol. Cell 2005, 20, 881-890.
34. Zhang, Y.; Kaplan-Lefko, P. J.; Rex, K.; Yang, Y.; Moriguchi, J.; Osgood, T; Mattson, B.; Coxon, A.; Reese, M.; Kim, T. S.; Lin, J.; Chen, A.; Burgess, T. L.; Dussault, I. Identification of a Novel Recepteur d'Origine Nantais/c-Met Small-Molecule Kinase Inhibitor with Antitumor Activity In vivo. Cancer Res. 2008, 68, 6680-6686.
35. Smolen, G. A.; Sordella, R.; Muir, B.; Mohapatra, G.; Barmettler, A.; Archibald, H.; Kim, W. J.; Okimoto, R. A.; Bell, D. W.; Sgroi, D. C.; Christensen, J. G.; Haber, D. A. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc. Natl. Acad. Sci. USA 2006, 103, 2316-2321.
36. Bache, K. G.; Slagsvold, T.; Stenmark, H. Defective downregulation of receptor tyrosine kinases in cancer. EMBO J. 2004, 23, 2707-2712.
37. Hudis, C. A.; Trastuzumab--mechanism of action and use in clinical practice. N. Engl. J. Med. 2007, 357, 39-51.
38. Spangler, J. B.; Neil, J. R.; Abramovitch, S.; Yarden, Y.; White, F. M.; Lauffenburger, D. A.; Wittrup, K. D.; Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling. Proc. Nat. Acad. Sci. USA 2010, 107, 13252-13257.
39. Ablain, J.; Nasr, R.; Bazarbachi, A.; de Thé. H. The Drug-Induced Degradation of Oncoproteins: An Unexpected Achilles' Heel of Cancer Cells? Cancer Discov. 2011, 1, 117-127.