Inhibition of MUC1-C suppresses MYC expression and attenuates malignant growth in KRAS mutant lung adenocarcinomas

Cancer Research

Volumn 76, Issue 6, 2016, Pages 1538-1548

  Bouillez, Audrey ^a   Rajabi, Hasan ^a   Pitroda, Sean ^b   Jin, Caining ^a   Alam, Maroof ^a   Kharbanda, Akriti ^a,c   Tagde, Ashujit ^a   Wong, Kwok Kin ^a   Kufe, Donald ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 CHLOROPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETIC ACID TERT BUTYL ESTER; BETA CATENIN; CRISPR ASSOCIATED PROTEIN; CYCLIN DEPENDENT KINASE 4; GO 203; HISTONE ACETYLTRANSFERASE PCAF; HISTONE H3; MUC1 C PROTEIN; MUCIN 1; MYC PROTEIN; PROTEIN INHIBITOR; REGULATOR PROTEIN; SHORT HAIRPIN RNA; TCF4 PROTEIN; TELOMERASE REVERSE TRANSCRIPTASE; UNCLASSIFIED DRUG; WNT PROTEIN; (ARGININE)9-CYSTEINYL-GLUTAMINYL-CYSTEINYL-ARGINYL-ARGINYL-LYSYL-ASPARAGINE; E1A ASSOCIATED P300 PROTEIN; EP300 PROTEIN, HUMAN; KRAS PROTEIN, HUMAN; MUC1 PROTEIN, HUMAN; PEPTIDE; PROTEIN P21; SMALL INTERFERING RNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER GROWTH; CELL SURVIVAL; COMPLEX FORMATION; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG POTENTIATION; FEMALE; GENE MUTATION; GENE SILENCING; GENE TARGETING; HISTONE ACETYLATION; HUMAN; HUMAN CELL; KRAS GENE; LUNG ADENOCARCINOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; ONCOGENE MYC; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; TRANSCRIPTION INITIATION; TUMOR XENOGRAFT; ADENOCARCINOMA; ANIMAL; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HEK293 CELL LINE; LUNG NEOPLASMS; MUTATION; NUDE MOUSE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ADENOCARCINOMA; ANIMALS; BETA CATENIN; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE; CELL LINE, TUMOR; CELL SURVIVAL; E1A-ASSOCIATED P300 PROTEIN; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HEK293 CELLS; HUMANS; LUNG NEOPLASMS; MICE, NUDE; MUCIN-1; MUTATION; PEPTIDES; PROTO-ONCOGENE PROTEINS C-MYC; PROTO-ONCOGENE PROTEINS P21(RAS); RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; WNT PROTEINS;

EID: 84962068352     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-15-1804     Document Type: Article

References (50)

1. Dang CV MYC on the path to cancer. Cell 2012; 149: 22-35.
2. Li B, Simon MC. Molecular pathways: targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer. Clin Cancer Res 2013; 19: 5835-41.
3. Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, et al. The landscape of somatic copy-number alteration across human cancers. Nature 2010; 463: 899-905.
4. Leder A, Pattengale PK, Kuo A, Stewart TA, Leder P. Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell 1986; 45: 485-95.
5. Arvanitis C, Felsher DW. Conditional transgenic models define how MYC initiates and maintains tumorigenesis. Semin Cancer Biol 2006; 16: 313-7.
6. Soucek L, Whitfield J, Martins CP, Finch AJ, Murphy DJ, Sodir NM, et al. Modelling Myc inhibition as a cancer therapy. Nature 2008; 455: 679-83.
7. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011; 146: 904-17.
8. Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011; 478: 524-8.
9. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature 2010; 468: 1067-73.
10. Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G, et al. A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol 2004; 6: 308-18.
11. Soucek L, Whitfield JR, Sodir NM, Masso-Valles D, Serrano E, Karnezis AN, et al. Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice. Genes Dev 2013; 27: 504-13.
12. Fukazawa T, Maeda Y, Matsuoka J, Yamatsuji T, Shigemitsu k, Morita I, et al. Inhibition of Myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc. Anticancer Res 2010; 30: 4193-200.
13. Shimamura T, Chen Z, Soucheray M, Carretero J, Kikuchi E, Tchaicha JH, et al. Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer. Clin Cancer Res 2013; 19: 6183-92.
14. Situ D, Wang J, Ma Y, Zhu Z, Hu Y, Long H, et al. Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer. Med Oncol 2010; 28: 596-604.
15. Khodarev N, Pitroda S, Beckett M, MacDermed D, Huang L, Kufe D, et al. MUC1-induced transcriptional programs associated with tumorigenesis predict outcome in breast and lung cancer. Cancer Res 2009; 69: 2833-7.
16. MacDermed DM, Khodarev NN, Pitroda SP, Edwards DC, Pelizzari CA, Huang L, et al. MUC1-associated proliferation signature predicts outcomes in lung adenocarcinoma patients. BMC Medical Genomics 2010; 3: 16.
17. Kufe D. Mucins in cancer: function, prognosis and therapy. Nature Reviews Cancer 2009; 9: 874-85.
18. Kufe D. MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches. Oncogene 2013; 32: 1073-81.
19. Yamamoto M, Bharti A, Li Y, Kufe D. Interaction of the DF3/MUC1 breast carcinoma-associated antigen and b-catenin in cell adhesion. J Biol Chem 1997; 272: 12492-4.
20. Huang L, Chen D, Liu D, Yin L, Kharbanda S, Kufe D. MUC1 oncoprotein blocks GSK3b-mediated phosphorylation and degradation of b-catenin. Cancer Res 2005; 65: 10413-22.
21. Rajabi H, Ahmad R, Jin C, Kosugi M, Alam M, Joshi M, et al. MUC1-C oncoprotein induces TCF7L2 activation and promotes cyclin D1 expression in human breast cancer cells. J Biol Chem 2012; 287: 10703-13.
22. Leng Y, Cao C, Ren J, Huang L, Chen D, Ito M, et al. Nuclear import of the MUC1-C oncoprotein is mediated by nucleoporin Nup62. J Biol Chem 2007; 282: 19321-30.
23. Raina D, Ahmad R, Rajabi H, Panchamoorthy G, Kharbanda S, Kufe D. Targeting cysteine-mediated dimerization of the MUC1-C oncoprotein in human cancer cells. Int J Oncol 2012; 40: 1643-9.
24. Kufe D. Functional targeting of the MUC1 oncogene in human cancers. Cancer Biol Ther 2009; 8: 1201-7.
25. Raina D, Kosugi M, Ahmad R, Panchamoorthy G, Rajabi H, Alam M, et al. Dependence on the MUC1-C oncoprotein in non-small cell lung cancer cells. Mol Cancer Therapeutics 2011; 10: 806-16.
26. Kharbanda A, Rajabi H, Jin C, Alam M, Wong K, Kufe D. MUC1-C confers EMT and KRAS independence in mutant KRAS lung cancer cells. Oncotarget 2014; 5: 8893-905.
27. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013; 339: 819-23.
28. Rajabi H, Alam M, Takahashi H, Kharbanda A, Guha M, Ahmad R, et al. MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition. Oncogene 2014; 33: 1680-9.
29. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science 1998; 281: 1509-12.
30. Alam M, Ahmad R, Rajabi H, Kharbanda A, Kufe D. MUC1-C oncoprotein activates ERK!C/EBPb-mediated induction of aldehyde dehydrogenase activity in breast cancer cells. J Biol Chem 2013; 288: 30829-903.
31. Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/-colon carcinoma. Science 1997; 275: 1784-7.
32. Brannon M, Brown JD, Bates R, Kimelman D, Moon RT. XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development. Development 1999; 126: 3159-70.
33. Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, et al. Identification of a Wnt/Dvl/beta-Catenin! Pitx2 pathway mediating cell-type-specific proliferation during development. Cell 2002; 111: 673-85.
34. Daniels DL, Weis WI. Beta-catenin directly displaces Groucho/TLE repres-sors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol 2005; 12: 364-71.
35. Evans PM, Chen X, Zhang W, Liu C. KLF4 interacts with beta-catenin/TCF4 and blocks p300/CBP recruitment by beta-catenin. Mol Cell Biol 2010; 30: 372-81.
36. Wu KJ, Grandori C, Amacker M, Simon-Vermot N, Polack A, Lingner J, et al. Direct activation of TERT transcription by c-MYC. Nat Genet 1999; 21: 220-4.
37. Hermeking H, Rago C, Schuhmacher M, Li Q, Barrett JF, Obaya AJ, et al. Identification of CDK4 as a target of c-MYC. Proc Natl Acad Sci U S A 2000; 97: 2229-34.
38. Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer 2011; 11: 761-74.
39. Bretones G, Delgado MD, Leon J. Myc and cell cycle control. Biochim Biophys Acta 2015; 1849: 506-16.
40. Conacci-Sorrell M, McFerrin L, Eisenman RN. An overview of MYC and its interactome. Cold Spring Harbor Perspectives in Medicine 2014; 4: a014357.
41. Raina D, Agarwal P, Lee J, Bharti A, McKnight C, Sharma P, et al. Characterization of the MUC1-C cytoplasmic domain as a cancer target. PLoS One 2015; 10:e0135156.
42. Gsponer J, Babu MM. The rules of disorder or why disorder rules. Progress in Biophysics and Molecular Biology 2009; 99: 94-103.
43. Huang L, Ren J, Chen D, Li Y, Kharbanda S, Kufe D. MUC1 cytoplasmic domain coactivates Wnt target gene transcription and confers transformation. Cancer Biol Ther 2003; 2: 702-6.
44. Hattrup CL, Gendler SJ. MUC1 alters oncogenic events and transcription in human breast cancer cells. Breast Cancer Res 2006; 8:R37.
45. Dang CV, O'Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F. The c-Myc target gene network. Semin Cancer Biol 2006; 16: 253-64.
46. Wang J, Xie LY, Allan S, Beach D, Hannon GJ. Myc activates telomerase. Genes Dev 1998; 12: 1769-74.
47. Kendall SD, Adam SJ, Counter CM. Genetically engineered human cancer models utilizing mammalian transgene expression. Cell Cycle 2006; 5: 1074-9.
48. Puyol M, Martin A, Dubus P, Mulero F, Pizcueta P, Khan G, et al. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell 2010; 18: 63-73.
49. McKeown MR, Bradner JE. Therapeutic strategies to inhibit MYC. Cold Spring Harbor Perspectives in Medicine 2014; 4: 1-16.
50. Hasegawa M, Sinha RK, Kumar M, Alam M, Yin L, Raina D, et al. Intracellular Targeting of the Oncogenic MUC1-C Protein with a Novel GO-203 Nanoparticle Formulation. Clin Cancer Res 2015; 21: 2338-47.