Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors

Cancer Research

Volumn 73, Issue 3, 2013, Pages 1190-1200

  Chakrabarty, Anindita ^a   Bhola, Neil E ^b   Sutton, Cammie ^b   Ghosh, Ritwik ^b   Kuba, María Gabriela ^c   Dave, Bhuvanesh ^e   Chang, Jenny C ^e   Arteaga, Carlos L ^a,b,d,f  

^a Departments of Cancer Biology   (United States)

^b VANDERBILT UNIVERSITY   (United States)

^c Departments of Pathology   (United States)

^d VANDERBILT INGRAM CANCER CENTER   (United States)

^e HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^f VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DEHYDROGENASE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; INTERLEUKIN 8; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SURVIVIN; TRANSCRIPTION FACTOR FOXO; TRASTUZUMAB; XL 147;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BIRC5 GENE; BREAST CANCER; CANCER RESISTANCE; CELL PROLIFERATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DOWN REGULATION; DRUG EFFECT; DRUG MECHANISM; DRUG RESPONSE; FEMALE; GENE IDENTIFICATION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA INTERFERENCE; SIGNAL TRANSDUCTION;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; DRUG RESISTANCE, NEOPLASM; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; INHIBITOR OF APOPTOSIS PROTEINS; MICE; NEOPLASTIC STEM CELLS; PHOSPHATIDYLINOSITOL 3-KINASES; RECEPTOR, ERBB-2;

EID: 84873445750     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-2440     Document Type: Article

References (49)

1. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 2000;19:3159-67.
2. Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene 2007; 26:6469-87.
3. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235: 177-82.
4. Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF III, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A 2003;100:8933-8.
5. Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, et al. A central role of HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res 2008;68:5878-87.
6. Yakes FM, Chinratanalab W, Ritter CA, King W, Seelig S, Arteaga CL. Herceptin-induced inhibition of phosphatidylinositol-3 kinase and AKT is required for antibody-mediated effects on p27, Cyclin D1, and antitumor action. Cancer Res 2002;62:4132-41.
7. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 1992;89:4285-9.
8. Stern HM. Improving treatment of HER2-positive cancers: opportunities and challenges. Sci Transl Med 2012;4:127rv2.
9. Nahta R, Esteva FJ. Trastuzumab: triumphs and tribulations. Oncogene 2007;26:3637-43.
10. Nagata Y, Lan K-H, 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;6:117-27.
11. Kataoka Y, Mukohara T, Shimada H, Saijo N, Hirai M, Minami H. Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines. Ann Oncol 2010;21:255-62.
12. Eichhorn PJ, Gili M, Scaltriti M, Serra V, Guzman M, Nijkamp W, et al. Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer Res 2008;68:9221-30.
13. Junttila TT, Akita RW, Parsons K, Fields C, Phillips GDL, Friedman LS, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-GDC-0941. Cancer Cell 2009;15:429-40.
14. Tsang RY, Finn RS. Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer. Br J Cancer 2012;106: 6-13.
15. Edelman G, Bedell C, Shapiro G, Pandya SS, Kwak EL, Scheffold C, et al. A phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies. J Clin Oncol 2010;28:3004.
16. McDermott SP, Wicha MS. Targeting breast cancer stem cells. Mol Oncol 2010;4:404-19.
17. Ritter CA, Perez-Torres M, Rinehart C, Guix M, Dugger T, Engelman JA, et al. Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network. Clin Cancer Res 2007;13:4909-19.
18. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999;96:857-68.
19. Wang SE, Narasanna A, Perez-Torres M, Xiang B, WuFY, Yang S, et al. HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Cancer Cell 2006;10:25-38.
20. Balko JM, Miller TW, Morrison MM, Hutchinson K, Young C, Rinehart C, et al. The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc Natl Acad Sci U S A 2012;109:221-6.
21. Chakrabarty A, Rexer BN, Wang SE, Cook RS, Engelman JA, Arteaga CL. H1047R phosphatidylinositol 3-kinase mutant enhances HER2-mediated transformation by heregulin production and activation of HER3. Oncogene 2010;29:5193-203.
22. Chakrabarty A, Sanchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci USA 2012; 109:2718-23.
23. Allen LF, Sebolt-Leopold J, Meyer MB. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol 2003;30:105-16.
24. Weigelt B, Warne PH, Downward J. PIK3CA mutation, but not PTEN loss of function, determines the sensitivity of breast cancer cells to mTOR inhibitory drugs. Oncogene 2011;30:3222-33.
25. Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011;19:58-71.
26. Izumi Y, Xu L, di Tomaso E, Fukumura D, Jain RK. Tumour biology: herceptin acts as an anti-angiogenic cocktail. Nature 2002;416: 279-80.
27. Karadedou CT, Gomes AR, Chen J, Petkovic M, Ho KK, Zwolinska AK, et al. FOXO3a repressesVEGF expression through FOXM1-dependent and -independent mechanisms in breast cancer. Oncogene 2012;31: 1845-58.
28. Voliva CF, Pecchi S, Burger M, Nagel T, Schnell C, Fritsch C, et al. Biological characterization of NVP-BKM120, a novel inhibitor of phosphoinosotide 3-kinase in Phase I/II clinical trials [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; 2010. Abstract no. 4498, poster session: 25, session category: Experimental and Molecular Therapeutics 34.
29. Maira SM, Stuffer F, Brueggen J, Furet P, Schnell C, Fritsch C, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008;7:1851-63.
30. Korkaya H, Paulson A, Iovino F, Wicha MS. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 2008;27:6120-30.
31. Magnifico A, Albano L, Campaner S, Delia D, Castiglioni F, Gasparini P, et al. Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab. Clin Cancer Res 2009;15:2010-21.
32. Nakshatri H, Srour E, Badve S. Breast cancer stem cells and intrinsic subtypes: controversies rage on. Curr Stem Cell Res Ther 2009;4: 50-60.
33. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007;1:555-67.
34. Charafe-Jauffret E, Ginestier C, Iovino F, Wicinski J, Cervera N, Finetti P, et al. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res 2009;69:1302-13.
35. Potente M, Urbich C, Sasaki K, Hofmann WK, Heeschen C, Aicher A, et al. Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Invest 2005;115: 2382-92.
36. Snoeks L, Weber CR, Turner JR, Bhattacharyya M, Wasland K, Savkovic SD. Tumor suppressor Foxo3a is involved in the regulation of lipopolysaccharide- induced interleukin-8 in intestinal HT-29 cells. Infect Immun 2008;76:4677-85.
37. Myatt SS, Lam EW-F. The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 2007;7:847-59.
38. Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer 2008;8:61-70.
39. Guha M, Plescia J, Leav I, Li J, Languino LR, Altieri DC. Endogenous tumor suppression mediated by PTENinvolves survivin gene silencing. Cancer Res 2009;69:4954-8.
40. Obexer P, Hagenbuchner J, Unterkircher T, Sachsenmaier N, Seifarth C, Bock G, et al. Repression of BIRC5/survivin by FOXO3/FKHRL1 sensitizes human neuroblastoma cells to DNA damage-induced apoptosis. Mol Biol Cell 2009;20:2041-8.
41. Nakahara T, Kita A, Yamanaka K, Mori M, Amino N, Takeuchi M, et al. Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer Sci 2011;102: 614-21.
42. Lee CW, Simin K, Liu Q, Plescia J, Guha M, Khan A, et al. A functional Notch-survivin gene signature in basal breast cancer. Breast Cancer Res 2008;10:R97.
43. Leung CG, Xu Y, Mularski B, Liu H, Gurbuxani S, Crispino JD. Requirements for survivin in terminal differentiation of erythroid cells and maintenance of hematopoietic stem and progenitor cells. J Exp Med 2007;204:1603-11.
44. Martelli AM, Faenza I, Billi AM, Manzoli L, Evangelisti C, Fal-a F, et al. Intranuclear 30-phosphoinositide metabolism and Akt signaling: new mechanisms for tumorigenesis and protection against apoptosis? Cell Signal 2006;18:1101-7.
45. Dave B, Migliaccio I, Gutierrez MC, Wu M-F, Chamness GC, Wong H, et al. Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2-overexpressing locally advanced breast cancers. J Clin Oncol 2011;29:166-73.
46. Diehn M, Cho RW, Clarke MF. Therapeutic implications of the cancer stem cell hypothesis. Semin Radiat Oncol 2009;19:78-86.
47. Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 2010;120:485-97.
48. Faber AC, Li D, Song Y, Liang MC, Yeap BY, Bronson RT, et al. Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition. Proc Natl Acad Sci U S A 2009;106:19503-8.
49. Ryan BM, Konecny GE, Kahlert S, Wang HJ, Untch M, Meng G, et al. Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol 2006;17:597-604.