RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer

Cancer Research

Volumn 72, Issue 19, 2012, Pages 5025-5034

  Patel, Ronil A ^a   Forinash, Kara D ^a   Pireddu, Roberta ^a   Sun, Ying ^a   Sun, Nan ^a   Martin, Mathew P ^a   Schönbrunn, Ernst ^a,b   Lawrence, Nicholas J ^a,b   Sebti, Saïd M ^a,b  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF SOUTH FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BRADYKININ; MITOGEN ACTIVATED PROTEIN KINASE; PLATELET DERIVED GROWTH FACTOR; PROTEIN KINASE B; RHO KINASE; RHO KINASE INHIBITOR; RHO KINASE ROCK1; RHO KINASE ROCK2; RKI 1313; RKI 1447; S6 KINASE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CANCER INHIBITION; CANCER INVASION; CELL MIGRATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOSKELETON; DRUG EFFECT; DRUG EFFICACY; DRUG PROTEIN BINDING; DRUG RESEARCH; ENZYME PHOSPHORYLATION; ENZYME REPRESSION; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; LAMELLIPODIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN FUNCTION; PROTEIN MOTIF;

ANIMALS; ANTINEOPLASTIC AGENTS; BINDING SITES; BLOTTING, WESTERN; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL MOVEMENT; CRYSTALLOGRAPHY, X-RAY; CYTOSKELETON; HUMANS; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MICE, TRANSGENIC; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NEOPLASM INVASIVENESS; NIH 3T3 CELLS; PROTEIN BINDING; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; RHO-ASSOCIATED KINASES; SUBSTRATE SPECIFICITY; THIAZOLES; TUMOR BURDEN; UREA;

EID: 84867120378     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-0954     Document Type: Article

References (54)

1. Bernards A. GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila. Biochim Biophys Acta 2003;1603:47-82. (Pubitemid 36262941)
2. DerMardirossian C, Bokoch GM. GDIs: central regulatory molecules in Rho GTPase activation. Trends Cell Biol 2005;15:356-63. (Pubitemid 40943524)
3. Rossman KL, Der CJ, Sondek J. GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 2005;6:167-80. (Pubitemid 40215811)
4. Izawa I, Amano M, Chihara K, Yamamoto T, Kaibuchi K. Possible involvement of the inactivation of the Rho-Rho-kinase pathway in oncogenic Ras-induced transformation. Oncogene 1998;17:2863-71. (Pubitemid 29010056)
5. Clark EA, Golub TR, Lander ES, Hynes RO. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 2000;406:532-5. (Pubitemid 30625739)
6. Yoshioka K, Nakamori S, Itoh K. Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. Cancer Res 1999;59:2004-10. (Pubitemid 29186178)
7. Burbelo P, Wellstein A, Pestell RG. Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res Treat 2004;84:43-8. (Pubitemid 38388859)
8. Fritz G, Just I, Kaina B. Rho GTPases are over-expressed in human tumors. Int J Cancer 1999;81:682-7. (Pubitemid 29214373)
9. Ridley AJ. Rho proteins and cancer. Breast Cancer Res Treat 2004;84:13-9. (Pubitemid 38388856)
10. Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2002;2:133-42.
11. Kleer CG, van Golen KL, Zhang Y, Wu ZF, Rubin MA, Merajver SD. Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability. Am J Pathol 2002;160:579-84. (Pubitemid 34160335)
12. Suwa H, Ohshio G, Imamura T, Watanabe G, Arii S, Imamura M, et al. Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. Br J Cancer 1998;77:147-52. (Pubitemid 28029787)
13. Amano M, Fukata Y, Kaibuchi K. Regulation and functions of Rho-associated kinase. Exp Cell Res 2000;261:44-51.
14. Olson MF. Applications for ROCK kinase inhibition. Curr Opin Cell Biol 2008;20:242-8.
15. Redowicz MJ. Rho-associated kinase: involvement in the cytoskeleton regulation. Arch Biochem Biophys 1999;364:122-4. (Pubitemid 29394299)
16. Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003;4:446-56. (Pubitemid 36648590)
17. Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 2003;83:1325-58. (Pubitemid 37222274)
18. Tang Y, Olufemi L, Wang MT, Nie D. Role of Rho GTPases in breast cancer. Front Biosci 2008;13:759-76. (Pubitemid 351599780)
19. Zicha D, Dobbie IM, Holt MR, Monypenny J, Soong DY, Gray C, et al. Rapid actin transport during cell protrusion. Science 2003;300:142-5. (Pubitemid 36423048)
20. Olson MF, Sahai E. The actin cytoskeleton in cancer cell motility. Clin Exp Metastasis 2009;26:273-87.
21. Scott RW, Olson MF. LIM kinases: function, regulation and association with human disease. J Mol Med (Berl) 2007;85:555-68. (Pubitemid 46870893)
22. Bourguignon LY, Zhu H, Shao L, Zhu D, Chen YW. Rho-kinase (ROK) promotes CD44v(3,8-10)-ankyrin interaction and tumor cell migration in metastatic breast cancer cells. Cell Motil Cytoskeleton 1999;43:269-87. (Pubitemid 29368201)
23. Itoh K, Yoshioka K, Akedo H, Uehata M, Ishizaki T, Narumiya S. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med 1999;5:221-5. (Pubitemid 29068531)
24. Li B, Zhao WD, Tan ZM, Fang WG, Zhu L, Chen YH. Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells. FEBS Lett 2006;580:4252-60. (Pubitemid 44037578)
25. Imamura F, Mukai M, Ayaki M, Akedo H. Y-27632, an inhibitor of rho-associated protein kinase, suppresses tumor cell invasion via regulation of focal adhesion and focal adhesion kinase. Jpn J Cancer Res 2000;91:811-6.
26. Liu S, Goldstein RH, Scepansky EM, Rosenblatt M. Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res 2009;69:8742-51.
27. Routhier A, Astuccio M, Lahey D, Monfredo N, Johnson A, Callahan W, et al. Pharmacological inhibition of Rho-kinase signaling with Y-27632 blocks melanoma tumor growth. Oncol Rep 2010;23:861-7.
28. Wyckoff JB, Pinner SE, Gschmeissner S, Condeelis JS, Sahai E. ROCK- and myosin-dependent matrix deformation enables protease-independent tumor-cell invasion in vivo. Curr Biol 2006;16:1515-23. (Pubitemid 44142977)
29. Ying H, Biroc SL, Li WW, Alicke B, Xuan JA, Pagila R, et al. The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models. Mol Cancer Ther 2006;5:2158-64. (Pubitemid 44530451)
30. Yoshioka K, Foletta V, Bernard O, Itoh K. A role for LIM kinase in cancer invasion. Proc Natl Acad Sci U S A 2003;100:7247-52. (Pubitemid 36706424)
31. Lane J, Martin TA, Watkins G, Mansel RE, Jiang WG. The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int J Oncol 2008;33:585-93.
32. Berndt N, Hamilton AD, Sebti SM. Targeting protein prenylation for cancer therapy. Nat Rev Cancer 2011;11:775-91.
33. O'Dwyer PJ, Gallagher M, Nguyen B, Waddell MJ, Chiorean EG. Phase I accelerated dose-escalating safety and pharmacokinetic (PK) study of GGTI-2418, a novel geranylgeranyltransferase I inhibitor in patients with refractory solid tumors. Ann Oncol 2010;21 (Suppl 2):ii42.
34. Pireddu R, Forinash KD, Sun NN, Martin MP, Sung SS, Alexander B, et al. Pyridylthiazole-based ureas as inhibitors of Rho associated protein kinases (ROCK1 and 2). Med Chem Commun 2012;3:699-709.
35. Kabsch W. Automatic processing of rotation diffraction data from crystals of initially unknown symmetry and cell constants. J Appl Cryst 1993;26:795-800.
36. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 1994;50:760-3.
37. Adams PD, Afonine PV, Bunkoczi G, Chen VB, Davis IW, Echols N, et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 2010;66(Pt 2):213-21.
38. Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 2004;60(Pt 12 Pt 1):2126-32.
39. Delano WL. PyMOL Molecular Graphics System. DeLano Scientific LLC, Palo Alto, CA, USA 2008.
40. Kazi A, Sun J, Doi K, Sung SS, Takahashi Y, Yin H, et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax-and Bim-dependentmanner. J Biol Chem2011;286:9382-92.
41. Balasis ME, Forinash KD, Chen YA, Fulp WJ, Coppola D, Hamilton AD, et al. Combination of farnesyltransferase and Akt inhibitors is synergistic in breast cancer cells and causes significant breast tumor regression in ErbB2 transgenic mice. Clin Cancer Res 2011;17:2852-62.
42. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
43. Strecker TE, Shen Q, Zhang Y, Hill JL, Li Y, Wang C, et al. Effect of lapatinib on the development of estrogen receptor-negative mammary tumors in mice. J Natl Cancer Inst 2009;101:107-13.
44. Lu C, Speers C, Zhang Y, Xu X, Hill J, Steinbis E, et al. Effect of epidermal growth factor receptor inhibitor on development of estrogen receptor-negative mammary tumors. J Natl Cancer Inst 2003;95:1825-33. (Pubitemid 38054683)
45. Rodrigues LM, Chung YL, Al Saffar NM, Sharp SY, Jackson LE, Banerji U, et al. Effects of HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on NEU/HER2 overexpressing mammary tumours in MMTV-NEUNT mice monitored by Magnetic Resonance Spectroscopy. BMC Res Notes 2012;5:250.
46. Roberts PJ, Bisi JE, Strum JC, Combest AJ, Darr DB, Usary JE, et al. Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J Natl Cancer Inst 2012;104:476-87.
47. Junutula JR, Flagella KM, Graham RA, Parsons KL, Ha E, Raab H, et al. Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2-positive breast cancer. Clin Cancer Res 2010;16:4769-78.
48. Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK, et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 2005;97:1254-61. (Pubitemid 41535366)
49. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res 2009;7:4-13.
50. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 2005;23:7721-35. (Pubitemid 46291836)
51. Bershtein LM, Alimova IN, Tsyrlina EV, Anisimov VN. Mammary tumors in HER-2/NEU mice are characterized by low content of estrogen receptors-alpha and absence of progesterone receptors. Bull Exp Biol Med 2003;135:580-1. (Pubitemid 37368989)
52. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133:704-15. (Pubitemid 351636299)
53. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010;29:4741-51.
54. Khamis ZI, Sahab ZJ, Sang QX. Active roles of tumor stroma in breast cancer metastasis. Int J Breast Cancer 2012;2012:574025.