Targeting the MUC1-C oncoprotein downregulates HER2 activation and abrogates trastuzumab resistance in breast cancer cells

Oncogene

Volumn 33, Issue 26, 2014, Pages 3422-3431

  Raina, D ^a   Uchida, Y ^b   Kharbanda, A ^b   Rajabi, H ^b   Panchamoorthy, G ^a   Jin, C ^b   Kharbanda, S ^a   Scaltriti, M ^c   Baselga, J ^c   Kufe, D ^b  

^a Department of Genus Oncology   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

breast cancer; HER2; HER3; MUC1; resistance; trastuzumab

Indexed keywords

ANTINEOPLASTIC AGENT; CYCLIN E; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GO 203; MUCIN 1; ONCOPROTEIN; PROTEIN KINASE B; PROTEIN P27; TRASTUZUMAB; UNCLASSIFIED DRUG; (ARGININE)9-CYSTEINYL-GLUTAMINYL-CYSTEINYL-ARGINYL-ARGINYL-LYSYL-ASPARAGINE; CYCLIN DEPENDENT KINASE INHIBITOR 1B; ERBB2 PROTEIN, HUMAN; LAPATINIB; MONOCLONAL ANTIBODY; MUC1 PROTEIN, HUMAN; PEPTIDE; QUINAZOLINE DERIVATIVE; SMALL INTERFERING RNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; BREAST CANCER CELL LINE; CANCER INHIBITION; CANCER PATIENT; CANCER RESISTANCE; CARBOXY TERMINAL SEQUENCE; CELL SURVIVAL; CLONOGENESIS; CONTROLLED STUDY; DOWN REGULATION; DRUG POTENTIATION; DRUG TARGETING; FEMALE; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; ANIMAL; BAGG ALBINO MOUSE; BIOSYNTHESIS; BREAST NEOPLASMS; CELL PROLIFERATION; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NUDE MOUSE; PHOSPHORYLATION; RNA INTERFERENCE; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN E; CYCLIN-DEPENDENT KINASE INHIBITOR P27; DOWN-REGULATION; DRUG RESISTANCE, NEOPLASM; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICE; MICE, INBRED BALB C; MICE, NUDE; MUCIN-1; PEPTIDES; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; QUINAZOLINES; RECEPTOR, ERBB-2; RNA INTERFERENCE; RNA, SMALL INTERFERING; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84901396865     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2013.308     Document Type: Article

References (47)

1. Slamon D, Clark G, Wong S, Levin W, Ullrich A, Mcguire W. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177-182.
2. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005; 5: 341-354.
3. Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas 3rd CF, Hynes NE. The ErbB2/ ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci USA 2003; 100: 8933-8938.
4. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 2009; 9: 463-475.
5. Junttila TT, Akita RW, Parsons K, Fields C, Lewis Phillips GD, Friedman LS et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell 2009; 15: 429-440.
6. Klapper LN, Waterman H, Sela M, Yarden Y. Tumor-inhibitory antibodies to HER-2/ ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res 2000; 60: 3384-3388.
7. Scaltriti M, Verma C, Guzman M, Jimenez J, Parra JL, Pedersen K et al. Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity. Oncogene 2009; 28: 803-814.
8. Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J et al. PKB/Akt mediates cellcycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med 2002; 8: 1145-1152.
9. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783-792.
10. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer Jr. CE, Davidson NE et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673-1684.
11. Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2009; 27: 5838-5847.
12. Nagata Y, Lan KH, Zhou X, Tan M, Esteva FJ, Sahin AA et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004; 6: 117-127.
13. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 2007; 12: 395-402.
14. Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW et al. Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med 2011; 17: 461-469.
15. Scaltriti M, Rojo F, Ocana A, Anido J, Guzman M, Cortes J et al. Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst 2007; 99: 628-638.
16. Nahta R, Yuan LX, Zhang B, Kobayashi R, Esteva FJ. Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. Cancer Res 2005; 65: 11118-11128.
17. Shattuck DL, Miller JK, Carraway III KL, Sweeney C. Met receptor contributes to trastuzumab resistance of Her2-overexpressing breast cancer cells. Cancer Res 2008; 68: 1471-1477.
18. Huang X, Gao L, Wang S, McManaman JL, Thor AD, Yang X et al. Heterotrimerization of the growth factor receptors erbB2, erbB3, and insulin-like growth factor-1 receptor in breast cancer cells resistant to herceptin. Cancer Res 2010; 70: 1204-1214.
19. Mittendorf EA, Wu Y, Scaltriti M, Meric-Bernstam F, Hunt KK, Dawood S et al. Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res 2009; 15: 7381-7388.
20. Scaltriti M, Eichhorn PJ, Cortes J, Prudkin L, Aura C, Jimenez J et al. Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients. Proc Natl Acad Sci USA 2011; 108: 3761-3766.
21. Nahta R, Takahashi T, Ueno NT, Hung MC, Esteva FJ. P27(kip1) down-regulation is associated with trastuzumab resistance in breast cancer cells. Cancer Res 2004; 64: 3981-3986.
22. Lee-Hoeflich ST, Pham TQ, Dowbenko D, Munroe X, Lee J, Li L et al. PPM1H is a p27 phosphatase implicated in trastuzumab resistance. Cancer Discov 2011; 1: 326-337.
23. Li Y, Yu W-H, Ren J, Huang L, Kharbanda S, Loda M et al. Heregulin targets g-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 protein. Mol Cancer Res 2003; 1: 765-775.
24. Kufe D. MUC1-C oncoprotein as a target in breast cancer: activation of signaling pathways and therapeutic approaches. Oncogene 2013; 32: 1073-1081.
25. Kufe D. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer 2009; 9: 874-885.
26. Duraisamy S, Kufe T, Ramasamy S, Kufe D. Evolution of the human MUC1 oncoprotein. Int J Oncol 2007; 31: 671-677.
27. 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 Ther 2011; 10: 806-816.
28. Li Y, Liu D, Chen D, Kharbanda S, Kufe D. Human DF3/MUC1 carcinoma-associated protein functions as an oncogene. Oncogene 2003; 22: 6107-6110.
29. 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: 10413-10422.
30. 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: 19321-19330.
31. Raina D, Ahmad R, Joshi M, Yin L, Wu Z, Kawano T et al. Direct targeting of the MUC1 oncoprotein blocks survival and tumorigenicity of human breast carcinoma cells. Cancer Res 2009; 69: 5133-5141.
32. 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: 1643-1649.
33. Scaltriti M, Serra V, Normant E, Guzman M, Rodriguez O, Lim AR et al. Antitumor activity of the Hsp90 inhibitor IPI-504 in HER2-positive trastuzumab-resistant breast cancer. Mol Cancer Ther 2011; 10: 817-824.
34. Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res 2008; 68: 5878-5887.
35. Viglietto G, Motti ML, Bruni P, Melillo RM, D'Alessio A, Califano D et al. Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med 2002; 8: 1136-1144.
36. Motti ML, De Marco C, Califano D, Fusco A, Viglietto G. Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer. Cell Cycle 2004; 3: 1074-1080.
37. Buck E, Eyzaguirre A, Brown E, Petti F, McCormack S, Haley JD et al. Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in nonsmall- cell lung, pancreatic, colon, and breast tumors. Mol Cancer Ther 2006; 5: 2676-2684.
38. 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.
39. Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH et al. A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res 2004; 64: 6652-6659.
40. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006; 66: 1630-1639.
41. Nahta R, Yuan LX, Du Y, Esteva FJ. Lapatinib induces apoptosis in trastuzumabresistant breast cancer cells: effects on insulin-like growth factor I signaling. Mol Cancer Ther 2007; 6: 667-674.
42. Fessler S, Wotkowicz M, Mahanta S, Bamdad C. MUC1* is a determinant of trastuzumab (Herceptin) resistance in breast cancer cells. Breast Cancer Res Treat 2009; 118: 113-124.
43. Mittendorf EA, Liu Y, Tucker SL, McKenzie T, Qiao N, Akli S et al. A novel interaction between HER2/neu and cyclin E in breast cancer. Oncogene 2010; 29: 3896-3907.
44. Li P, Li C, Zhao X, Zhang X, Nicosia SV, Bai W. P27(Kip1) stabilization and G(1) arrest by 1,25-dihydroxyvitamin D(3) in ovarian cancer cells mediated through down-regulation of cyclin E/cyclin-dependent kinase 2 and Skp1- Cullin-F-box protein/Skp2 ubiquitin ligase. J Biol Chem 2004; 279: 25260-25267.
45. Vermeer PD, Einwalter LA, Moninger TO, Rokhlina T, Kern JA, Zabner J et al. Segregation of receptor and ligand regulates activation of epithelial growth factor receptor. Nature 2003; 422: 322-326.
46. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984; 22: 27-55.
47. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res 2010; 70: 440-446.