Functional genetic screen identifies increased sensitivity to WEE1 inhibition in cells with defects in Fanconi anemia and HR pathways

Molecular Cancer Therapeutics

Volumn 14, Issue 4, 2015, Pages 865-876

  Aarts, Marieke ^a,c   Bajrami, Ilirjana ^a   Herrera Abreu, Maria T ^a   Elliott, Richard ^a   Brough, Rachel ^a   Ashworth, Alan ^a,d   Lord, Christopher J ^a   Turner, Nicholas C ^a,b  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b ROYAL MARSDEN HOSPITAL   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 ALLYL 1 [6 (1 HYDROXY 1 METHYLETHYL) 2 PYRIDINYL] 6 [4 (4 METHYL 1 PIPERAZINYL)ANILINO] 1H PYRAZOLO[3,4 D]PYRIMIDIN 3(2H) ONE; BRCA1 PROTEIN; BRCA2 PROTEIN; CARRIER PROTEIN; CHECKPOINT KINASE 1; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 2; DNA HELICASE; FANCONI ANEMIA GROUP E PROTEIN; HISTONE H2AX; MYT1 PROTEIN; NUCLEOSIDE; NUCLEOTIDE; PROTEIN; RAD50 PROTEIN; RAD52 PROTEIN; RAD54 PROTEIN; RECQL4 PROTEIN; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; WEE1 PROTEIN; BRIP1 PROTEIN, HUMAN; CELL CYCLE PROTEIN; DNA BINDING PROTEIN; FANCM PROTEIN, HUMAN; MYT1 PROTEIN, HUMAN; NUCLEAR PROTEIN; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; RNA HELICASE; TRANSCRIPTION FACTOR; WEE1 PROTEIN, HUMAN;

ARTICLE; CANCER THERAPY; CELL CYCLE S PHASE; CONTROLLED STUDY; DNA DAMAGE; DNA REPLICATION; DRUG SENSITIVITY; ENZYME INHIBITION; FANCONI ANEMIA; GENE SILENCING; GENETIC SCREENING; GENETIC TRANSFECTION; HOMOLOGOUS RECOMBINATION; MITOSIS; PRIORITY JOURNAL; PROTEIN DEPLETION; SENSITIVITY ANALYSIS; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; CELL LINE; DRUG EFFECTS; DRUG RESISTANCE; GENE EXPRESSION; GENETICS; HUMAN; METABOLISM; PHYSIOLOGICAL STRESS; RNA INTERFERENCE;

CELL CYCLE PROTEINS; CELL LINE; DNA HELICASES; DNA REPLICATION; DNA-BINDING PROTEINS; DRUG RESISTANCE; FANCONI ANEMIA; GENE EXPRESSION; HOMOLOGOUS RECOMBINATION; HUMANS; MITOSIS; NUCLEAR PROTEINS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTEIN-TYROSINE KINASES; RNA HELICASES; RNA INTERFERENCE; RNA, SMALL INTERFERING; STRESS, PHYSIOLOGICAL; TRANSCRIPTION FACTORS;

EID: 84946563138     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-14-0845     Document Type: Article

References (46)

1. Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature 2004;432: 316-23.
2. Aarts M, Linardopoulos S, Turner NC. Tumour selective targeting of cell cycle kinases for cancer treatment. Curr Opin Pharmacol 2013;13:529-35.
3. Parker LL, Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 1992;257:1955-7.
4. Watanabe N, BroomeM, Hunter T. Regulation of thehumanWEE1HuCDK tyrosine 15-kinase during the cell cycle. EMBO J 1995;14:1878-91.
5. Lindqvist A, Rodriguez-Bravo V,Medema RH. The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol 2009;185:193-202.
6. Beck H, Nahse-Kumpf V, Larsen MS, O'Hanlon KA, Patzke S, Holmberg C, et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol Cell Biol 2012;32:4226-36.
7. Dominguez-Kelly R, Martin Y, Koundrioukoff S, Tanenbaum ME, Smits VA, Medema RH, et al. Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. J Cell Biol 2011; 194:567-79.
8. Caretti V, Hiddingh L, Lagerweij T, Schellen P, Koken PW, HullemanE, et al. WEE1kinase inhibition enhances the radiation response of diffuse intrinsic pontine gliomas. Mol Cancer Ther 2013;12:141-50.
9. PosthumaDeBoer J, Wurdinger T, Graat HC, van Beusechem VW, Helder MN, van Royen BJ, et al. WEE1 inhibition sensitizes osteosarcoma to radiotherapy. BMC Cancer 2011;11:156.
10. Aarts M, Sharpe R, Garcia-Murillas I, Gevensleben H, Hurd MS, Shumway SD, et al. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. Cancer Discov 2012;2:524-39.
11. Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, et al. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol Ther 2010;9:514-22.
12. Hirai H, Iwasawa Y, Okada M, Arai T, Nishibata T, Kobayashi M, et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther 2009;8:2992-3000.
13. Carrassa L, Chila R, Lupi M, Ricci F, Celenza C, Mazzoletti M, et al. Combined inhibition of Chk1 and Wee1: in vitro synergistic effect translates to tumor growth inhibition in vivo. Cell Cycle 2012;11:2507-17.
14. Davies KD, Cable PL, Garrus JE, Sullivan FX, von Carlowitz I, Huerou YL, et al. Chk1 inhibition and Wee1 inhibition combine synergistically to impede cellular proliferation. Cancer Biol Ther 2011;12:788-96.
15. Guertin AD, Martin MM, Roberts B, Hurd M, Qu X, Miselis NR, et al. Unique functions of CHK1 and WEE1 underlie synergistic anti-tumor activity upon pharmacologic inhibition. Cancer Cell Int 2012;12:45.
16. Russell MR, Levin K, Rader J, Belcastro L, Li Y, Martinez D, et al. Combination therapy targeting the Chk1 and Wee1 kinases shows therapeutic efficacy in neuroblastoma. Cancer Res 2013;73:776-84.
17. Vriend LE, De Witt Hamer PC, Van Noorden CJ, Wurdinger T. WEE1 inhibition and genomic instability in cancer. Biochim Biophys Acta 2013;1836:227-35.
18. Wilson PM, Labonte MJ, Russell J, Louie S, Ghobrial AA, Ladner RD. A novel fluorescence-based assay for the rapid detection and quantification of cellular deoxyribonucleoside triphosphates. Nucleic Acids Res 2011;39: e112.
19. Whitby MC. The FANCM family of DNA helicases/translocases. DNA Repair 2010;9:224-36.
20. Suhasini AN, Sommers JA, Muniandy PA, Coulombe Y, Cantor SB, Masson JY, et al. Fanconi anemia group J helicase and MRE11 nuclease interact to facilitate the DNA damage response. Mol Cell Biol 2013; 33:2212-27.
21. Wesoly J, Agarwal S, Sigurdsson S, Bussen W, Van Komen S, Qin J, et al. Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis. Mol Cell Biol 2006;26: 976-89.
22. Thangavel S, Mendoza-Maldonado R, Tissino E, Sidorova JM, Yin J, Wang W, et al. Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol Cell Biol 2010;30:1382-96.
23. Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y. MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J 2009;28:3005-14.
24. Bridges KA, Hirai H, Buser CA, Brooks C, Liu H, Buchholz TA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res 2011;17:5638-48.
25. Mir SE, De Witt Hamer PC, Krawczyk PM, Balaj L, Claes A, Niers JM, et al. In silico analysis of kinase expression identifies WEE1 as a gatekeeper against mitotic catastrophe in glioblastoma. Cancer Cell 2010;18:244-57.
26. Sarcar B, Kahali S, Prabhu AH, Shumway SD, Xu Y, Demuth T, et al. Targeting radiation-induced G(2) checkpoint activation with the Wee-1 inhibitor MK-1775 in glioblastoma cell lines. Mol Cancer Ther 2011; 10:2405-14.
27. Dai Y, Grant S. Targeting Chk1 in the replicative stress response. Cell Cycle 2010;9:1025.
28. Sorensen CS, Syljuasen RG. Safeguarding genome integrity: the checkpoint kinases ATR, CHK1 and WEE1 restrain CDK activity during normal DNA replication. Nucleic Acids Res 2012;40:477-86.
29. Mueller PR, Coleman TR, Kumagai A, Dunphy WG. Myt1: a membraneassociated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science 1995;270:86-90.
30. Blackford AN, Schwab RA, Nieminuszczy J, Deans AJ, West SC, Niedzwiedz W. The DNA translocase activity of FANCM protects stalled replication forks. Hum Mol Genet 2012;21:2005-16.
31. Schwab RA, Blackford AN, Niedzwiedz W. ATR activation and replication fork restart are defective in FANCM-deficient cells. EMBO J 2010;29: 806-18.
32. Schwab RA, Nieminuszczy J, Shin-ya K, Niedzwiedz W. FANCJ couples replication past natural fork barriers with maintenance of chromatin structure. J Cell Biol 2013;201:33-48.
33. Beck H, Nahse V, Larsen MS, Groth P, Clancy T, Lees M, et al. Regulators of cyclin-dependent kinases are crucial formaintaining genome integrity in S phase. J Cell Biol 2010;188:629-38.
34. Guertin AD, Li J, Liu Y, Hurd MS, Schuller AG, Long B, et al. Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. Mol Cancer Ther 2013;12:1442-52.
35. D'Andrea AD. Susceptibility pathways in Fanconi's anemia and breast cancer. N Engl J Med 2010;362:1909-19.
36. Singh TR, Saro D, Ali AM, Zheng XF, Du CH, Killen MW, et al. MHF1-MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM. Mol Cell 2010;37:879-86.
37. Deans AJ, West SC. DNA interstrand crosslink repair and cancer. Nat Rev Cancer 2011;11:467-80.
38. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet 2007;39:165-7.
39. Seal S, Thompson D, Renwick A, Elliott A, Kelly P, Barfoot R, et al. Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 2006;38:1239-41.
40. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995;378:789-92.
41. Kumaraswamy E, Shiekhattar R. Activation of BRCA1/BRCA2-associated helicase BACH1 is required for timely progression through S phase. Mol Cell Biol 2007;27:6733-41.
42. Nikkila J, Parplys AC, Pylkas K, Bose M, Huo Y, Borgmann K, et al. Heterozygous mutations in PALB2 cause DNA replication and damage response defects. Nat Commun 2013;4:2578.
43. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2012;12:68-78.
44. Tu Do K, Wilsker D, Balasubramanian P, Zlott J, Jeong W, Lawrence SM, et al. Phase I trial of AZD1775 (MK1775), a wee1 kinase inhibitor, in patients with refractory solid tumors. JClin Oncol 32:5s, 2014 (suppl; abstr 2503).
45. Kim Y, Lach FP, Desetty R, Hanenberg H, Auerbach AD, Smogorzewska A. Mutations of the SLX4 gene in Fanconi anemia. Nat Genet 2011; 43:142-6.
46. Cybulski KE, Howlett NG. FANCP/SLX4: a Swiss army knife of DNA interstrand crosslink repair. Cell Cycle 2011;10:1757-63.