RacGAP1 is a novel downstream effector of E2F7-dependent resistance to doxorubicin and is prognostic for overall survival in squamous cell carcinoma

Molecular Cancer Therapeutics

Volumn 14, Issue 8, 2015, Pages 1939-1950

  Hazar Rethinam, Mehlika ^a   De Long, Lilia Merida ^a   Gannon, Orla M ^a   Boros, Samuel ^b   Vargas, Ana Cristina ^b   Dzienis, Marcin ^b   Mukhopadhyay, Pamela ^a,c   Saenz Ponce, Natalia ^a   Dantzic, Daniel D E ^a   Simpson, Fiona ^a   Saunders, Nicholas A ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

^b PRINCESS ALEXANDRA HOSPITAL   (Australia)

^c QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; 4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; 8 (6 METHOXY 3 PYRIDINYL) 3 METHYL 1 [4 (1 PIPERAZINYL) 3 (TRIFLUOROMETHYL)PHENYL] 1H IMIDAZO[4,5 C]QUINOLIN 2(3H) ONE; CISPLATIN; DOXORUBICIN; ETOPOSIDE; MESSENGER RNA; RAC PROTEIN; RACGAP1 PROTEIN; SHORT HAIRPIN RNA; TRANSCRIPTION FACTOR E2F7; UNCLASSIFIED DRUG; ANTINEOPLASTIC ANTIBIOTIC; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; GUANOSINE TRIPHOSPHATE; MGCRACGAP; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAC1 PROTEIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER PATIENT; CANCER PROGNOSIS; CANCER RESISTANCE; CANCER SURVIVAL; CELL DIFFERENTIATION; CELL VIABILITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG SENSITIVITY; DRUG TOLERANCE; FEMALE; GENE OVEREXPRESSION; GENE REPRESSION; GENE SILENCING; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSCRIPTOMIC PROFILING; TRANSCRIPTOMICS; TUMOR GROWTH; UPREGULATION; WESTERN BLOTTING; ANIMAL; CARCINOMA, SQUAMOUS CELL; DISEASE MODEL; DRUG RESISTANCE; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MORTALITY; PROGNOSIS; TUMOR CELL LINE;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; DOXORUBICIN; DRUG RESISTANCE, NEOPLASM; E2F7 TRANSCRIPTION FACTOR; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE KNOCKDOWN TECHNIQUES; GTPASE-ACTIVATING PROTEINS; GUANOSINE TRIPHOSPHATE; HUMANS; MICE; PHOSPHATIDYLINOSITOL 3-KINASES; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-AKT; RAC1 GTP-BINDING PROTEIN; RHOA GTP-BINDING PROTEIN;

EID: 84942107886     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-15-0076     Document Type: Article

References (50)

1. Shen B, Dong P, Li D, Gao S. Expression and function of ABCG2 in head and neck squamous cell carcinoma and cell lines. Exp Ther Med 2011;2:1151-7.
2. Li R, Zang Y, Li C, Patel NS, Grandis JR, Johnson DE. ABT-737 synergizes with chemotherapy to kill head and neck squamous cell carcinoma cells via a Noxa-mediated pathway. Mol Pharmacol 2009;75:1231-9.
3. Haddad R, Colevas AD, Tishler R, Busse P, Goguen L, Sullivan C, et al. Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck: the Dana Farber Cancer Institute experience. Cancer 2003;97:412-8.
4. Sharafinski ME, Ferris RL, Ferrone S, Grandis JR. Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck 2010;32:1412-21.
5. Hazar-Rethinam M, Endo-Munoz L, Gannon O, Saunders N. The role of the E2F transcription factor family in UV-induced apoptosis. Int J Mol Sci 2011;12:8947-60.
6. Johnson DG, Degregori J. Putting the oncogenic and tumor suppressive activities of E2F into context. Curr Mol Med 2006;6:731-8.
7. Wikonkal NM, Remenyik E, Knezevic D, Zhang W, Liu M, Zhao H, et al. Inactivating E2f1 reverts apoptosis resistance and cancer sensitivity in Trp53-deficient mice. Nat Cell Biol 2003;5:655-60.
8. Berton TR, Mitchell DL, Guo R, Johnson DG. Regulation of epidermal apoptosis and DNA repair by E2F1 in response to ultraviolet B radiation. Oncogene 2005;24:2449-60.
9. Panagiotis Zalmas L, Zhao X, Graham AL, Fisher R, Reilly C, Coutts AS, et al. DNA-damage response control of E2F7 and E2F8. EMBO Rep 2008;9:252-9.
10. Li J, Ran C, Li E, Gordon F, Comstock G, Siddiqui H, et al. Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev Cell 2008;14:62-75.
11. Wong CF, Barnes LM, Dahler AL, Smith L, Serewko-Auret MM, Popa C, et al. E2F modulates keratinocyte squamous differentiation: implications for E2F inhibition in squamous cell carcinoma. J Biol Chem 2003;278:28516-22.
12. Dicker AJ, Popa C, Dahler AL, Serewko MM, Hilditch-Maguire PA, Frazer IH, et al. E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes. Oncogene 2000;19:2887-94.
13. Kwong RA, Nguyen TV, Bova RJ, Kench JG, Cole IE, Musgrove EA, et al. Overexpression of E2F-1 is associated with increased disease-free survival in squamous cell carcinoma of the anterior tongue. Clin Cancer Res 2003;9:3705-11.
14. Endo-Munoz L, Dahler A, Teakle N, Rickwood D, Hazar-Rethinam M, Abdul-Jabbar I, et al. E2F7 can regulate proliferation, differentiation, and apoptotic responses in human keratinocytes: implications for cutaneous squamous cell carcinoma formation. Cancer Res 2009;69:1800-8.
15. Hazar-Rethinam M, Merida de Long L, Gannon O, Topkas E, Boros S, Vargas AC, et al. A novel E2F/Sphingosine kinase 1 axis regulates anthracycline response in squamous cell carcinoma. Clin Cancer Res 2015;21:417-27.
16. Erlich RB, Kherrouche Z, Rickwood D, Endo-Munoz L, Cameron S, Dahler A, et al. Preclinical evaluation of dual PI3K-mTOR inhibitors and histone deacetylase inhibitors in head and neck squamous cell carcinoma. Br J Cancer 2012;106:107-15.
17. Zhao KN, Gu W, Fang NX, Saunders NA, Frazer IH. Gene codon composition determines differentiation-dependent expression of a viral capsid gene in keratinocytes in vitro and in vivo. Mol Cell Biol 2005;25:8643-55.
18. Jones SJ, Dicker AJ, Dahler AL, Saunders NA. E2F as a regulator of keratinocyte proliferation: implications for skin tumor development. J Investig Dermatol 1997;109:187-93.
19. Endo-Munoz L, Cumming A, Rickwood D, Wilson D, Cueva C, Ng C, et al. Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases. Cancer Res 2010;70:7063-72.
20. Dicker AJ, Serewko MM, Dahler AL, Khanna KK, Kaur P, Li A, et al. Functional characterization of cultured cells derived from an intraepidermal carcinoma of the skin (IEC-1). Exp Cell Res 2000;258:352-60.
21. Erlich RB, Rickwood D, Coman WB, Saunders NA, Guminski A. Valproic acid as a therapeutic agent for head and neck squamous cell carcinomas. Cancer Chemother Pharmacol 2009;63:381-9.
22. Cameron SR, Dahler AL, Endo-Munoz LB, Jabbar I, Thomas GP, Leo PJ, et al. Tumor-initiating activity and tumor morphology of HNSCC is modulated by interactions between clonal variants within the tumor. Lab Invest 2010;90:1594-603.
23. Detre S, Saclani Jotti G, Dowsett M. A "quickscore" method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol 1995;48:876-8.
24. Pliarchopoulou K, Kalogeras KT, Kronenwett R, Wirtz RM, Eleftheraki AG, Batistatou A, et al. Prognostic significance of RACGAP1 mRNA expression in high-risk early breast cancer: a study in primary tumors of breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial. Cancer Chemother Pharmacol 2013;71:245-55.
25. Zhao WM, Fang G. MgcRacGAP controls the assembly of the contractile ring and the initiation of cytokinesis. Proc Natl Acad Sci U S A 2005;102:13158-63.
26. Sahai E. Mechanisms of cancer cell invasion. Curr Opin Genet Dev 2005;15:87-96.
27. Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, et al. Rac activation and inactivation control plasticity of tumor cell movement. Cell 2008;135:510-23.
28. Vega FM, Ridley AJ. Rho GTPases in cancer cell biology. FEBS Lett 2008;582:2093-101.
29. Yamazaki D, Kurisu S, Takenawa T. Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates. Oncogene 2009;28:1570-83.
30. Kawashima T, Hirose K, Satoh T, Kaneko A, Ikeda Y, Kaziro Y, et al. MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells. Blood 2000;96:2116-24.
31. Tonozuka Y, Minoshima Y, Bao YC, Moon Y, Tsubono Y, Hatori T, et al. A GTPase-activating protein binds STAT3 and is required for IL-6-induced STAT3 activation and for differentiation of a leukemic cell line. Blood 2004;104:3550-7.
32. Nishimura K, Oki T, Kitaura J, Kuninaka S, Saya H, Sakaue-Sawano A, et al. APC(CDH1) targets MgcRacGAP for destruction in the late M phase. PLoS ONE 2013;8:e63001.
33. Olson MF. Applications for ROCK kinase inhibition. Curr Opin Cell Biol 2008;20:242-8.
34. Zins K, Lucas T, Reichl P, Abraham D, Aharinejad S. A Rac1/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of primary human prostate cancer xenografts and prolongs survival in mice. PLoS ONE 2013;8:e74924.
35. Akbar H, Cancelas J, Williams DA, Zheng J, Zheng Y. Rational design and applications of a Rac GTPase-specific small molecule inhibitor. Methods Enzymol 2006;406:554-65.
36. Doki N, Kawashima T, Nomura Y, Tsuchiya A, Oneyama C, Akagi T, et al. Constitutive phosphorylation of a Rac GAP MgcRacGAP is implicated in v-Src-induced transformation of NIH3T3 cells. Cancer Sci 2009;100:1675-79.
37. Minoshima Y, Kawashima T, Hirose K, Tonozuka Y, Kawajiri A, Bao YC, et al. Phosphorylation by aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell 2003;4:549-60.
38. Wang SM, Ooi LL, Hui KM. Upregulation of Rac GTPase-activating protein 1 is significantly associated with the early recurrence of human hepatocellular carcinoma. Clin Cancer Res 2011;17:6040-51.
39. Iglesias-Bartolome R, Martin D, Gutkind JS. Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets. Cancer Discov 2013;3:722-5.
40. Seguin L, Liot C, Mzali R, Harada R, Siret A, Nepveu A, et al. CUX1 and E2F1 regulate coordinated expression of the mitotic complex genes Ect2, MgcRacGAP, and MKLP1 in S phase. Mol Cell Biol 2009;29:570-81.
41. Weijts BGMW, Bakker WJ, Cornelissen PWA, Liang K-H, Schaftenaar FH, Westendorp B, et al. E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1. EMBO J 2012;31:3871-84.
42. Ke HL, Ke RH, Li ST, Li B, Lu HT, Wang XQ. Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression. J Neurooncol 2013;113:327-32.
43. Liang Y, Liu M, Wang P, Ding X, Cao Y. Analysis of 20 genes at chromosome band 12q13: RACGAP1 and MCRS1 overexpression in nonsmall-cell lung cancer. Genes Chromosomes Cancer 2013;52:305-15.
44. Saigusa S, Tanaka K, Mohri Y, Ohi M, Shimura T, Kitajima T, et al. Clinical significance of RacGAP1 expression at the invasive front of gastric cancer. Gastric Cancer 2015;18:84-92.
45. Lu KH, Patterson AP, Wang L, Marquez RT, Atkinson EN, Baggerly KA, et al. Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res 2004;10:3291-300.
46. Rosty C, Sheffer M, Tsafrir D, Stransky N, Tsafrir I, Peter M, et al. Identification of a proliferation gene cluster associated with HPV E6/E7 expression level and viral DNA load in invasive cervical carcinoma. Oncogene 2005;24:7094-104.
47. Ma XJ, Salunga R, Tuggle JT, Gaudet J, Enright E, McQuary P, et al. Gene expression profiles of human breast cancer progression. Proc Natl Acad Sci U S A 2003;100:5974-9.
48. Velaithan R, Kang J, Hirpara JL, Loh T, Goh BC, Le Bras M, et al. The small GTPase Rac1 is a novel binding partner of Bcl-2 and stabilizes its antiapoptotic activity. Blood 2011;117:6214-26.
49. Skvortsov S, Dudas J, Eichberger P, Witsch-Baumgartner M, Loeffler-Ragg J, Pritz C, et al. Rac1 as a potential therapeutic target for chemo-radioresistant head and neck squamous cell carcinomas (HNSCC). Br J Cancer 2014;110:2677-87.
50. Jacquemet G, Green DM, Bridgewater RE, von Kriegsheim A, Humphries MJ, Norman JC, et al. RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1-IQGAP1 complex. J Cell Biol 2013;202:917-35.