ERK2-dependent reactivation of Akt mediates the limited response of tumor cells with constitutive K-RAS activity to PI3K inhibition

Cancer Biology and Therapy

Volumn 15, Issue 3, 2014, Pages 317-328

  Toulany, Mahmoud ^a   Minjgee, Minjmaa ^a   Saki, Mohammad ^a   Holler, Marina ^a   Meier, Friedegund ^a   Eicheler, Wolfgang ^b   Rodemann, H Peter ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

Author keywords

EGFR; Erlotinib; HNSCC; K RAS; MAPK ERK; NSCLC; PI 103; PI3K Akt

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 (4 HYDROXYPHENYL) 4 MORPHOLINOPYRIDO[3',2':4,5]FURO[3,2 D]PYRIMIDINE; AMPHIREGULIN; CETUXIMAB; ERLOTINIB; K RAS PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN P53; 2-(2-AMINO-3-METHOXYPHENYL)-4H-1-BENZOPYRAN-4-ONE; EGFR PROTEIN, HUMAN; EPIDERMAL GROWTH FACTOR RECEPTOR; FLAVONOID; FURAN DERIVATIVE; KRAS PROTEIN, HUMAN; MAPK1 PROTEIN, HUMAN; ONCOPROTEIN; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINAZOLINE DERIVATIVE; RAS PROTEIN;

ARTICLE; CLONOGENESIS; CONTROLLED STUDY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME REACTIVATION; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; LUNG NON SMALL CELL CANCER; ANTAGONISTS AND INHIBITORS; CELL CLONE; CELL PROLIFERATION; CELL SURVIVAL; DRUG EFFECTS; DRUG POTENTIATION; GENETICS; HEAD AND NECK TUMOR; LUNG TUMOR; METABOLISM; NON SMALL CELL LUNG CANCER; PATHOLOGY; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; TUMOR CELL LINE;

CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; CLONE CELLS; DRUG SYNERGISM; FLAVONOIDS; FURANS; HEAD AND NECK NEOPLASMS; HUMANS; LUNG NEOPLASMS; MITOGEN-ACTIVATED PROTEIN KINASE 1; ONCOGENE PROTEIN V-AKT; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS; PYRIDINES; PYRIMIDINES; QUINAZOLINES; RAS PROTEINS; RECEPTOR, EPIDERMAL GROWTH FACTOR; SIGNAL TRANSDUCTION;

EID: 84896505123     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.27311     Document Type: Article

References (39)

1. 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; PMID:20848399; http://dx.doi.org/10.1002/hed.21365
2. Rodemann HP, Dittmann K, Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol 2007; 83:781-91; PMID:18058366; http://dx.doi.org/10.1080/09553000701769970 (Pubitemid 350219102)
3. Chen G, Noor A, Kronenberger P, Teugels E, Umelo IA, De Grève J. Synergistic effect of afatinib with su11274 in non-small cell lung cancer cells resistant to gefitinib or erlotinib. PLoS One 2013; 8:e59708; PMID:23527257; http://dx.doi.org/10.1371/journal. pone.0059708
4. Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res 2011; 17:1616-22; PMID:21135146; http://dx.doi.org/10.1158/1078-0432.CCR-10-2692
5. Eberhard DA, Johnson BE, Amler LC, Goddard AD, Heldens SL, Herbst RS, Ince WL, Jänne PA, Januario T, Johnson DH, et al. Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-smallcell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 2005; 23:5900-9; PMID:16043828; http://dx.doi.org/10.1200/JCO.2005.02.857
6. Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359:1757-65; PMID:18946061; http://dx.doi.org/10.1056/NEJMoa0804385
7. Wu YL, Zhong WZ, Li LY, Zhang XT, Zhang L, Zhou CC, Liu W, Jiang B, Mu XL, Lin JY, et al. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol 2007; 2:430-9; PMID:17473659; http://dx.doi.org/10.1097/01. JTO.0000268677.87496.4c (Pubitemid 47181698)
8. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304:1497-500; PMID:15118125; http://dx.doi.org/10.1126/science.1099314 (Pubitemid 38720929)
9. Nguyen KS, Kobayashi S, Costa DB. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 2009; 10:281-9; PMID:19632948; http://dx.doi.org/10.3816/CLC.2009.n.039
10. Ludovini V, Bianconi F, Pistola L, Chiari R, Minotti V, Colella R, Giuffrida D, Tofanetti FR, Siggillino A, Flacco A, et al. Phosphoinositide-3- kinase catalytic alpha and KRAS mutations are important predictors of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. J Thorac Oncol 2011; 6:707-15; PMID:21258250; http://dx.doi.org/10.1097/JTO.0b013e31820a3a6b
11. Yamamoto H, Shigematsu H, Nomura M, Lockwood WW, Sato M, Okumura N, Soh J, Suzuki M, Wistuba II, Fong KM, et al. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 2008; 68:6913-21; PMID:18757405; http://dx.doi.org/10.1158/0008-5472.CAN-07-5084
12. Bissada E, Abboud O, Abou Chacra Z, Guertin L, Weng X, Nguyen-Tan PF, Tabet JC, Thibaudeau E, Lambert L, Audet ML, et al. Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes. Int J Otolaryngol 2013; 2013:848021; PMID:23737793; http://dx.doi.org/10.1155/2013/848021
13. Hama T, Yuza Y, Suda T, Saito Y, Norizoe C, Kato T, Moriyama H, Urashima M. Functional mutation analysis of EGFR family genes and corresponding lymph node metastases in head and neck squamous cell carcinoma. Clin Exp Metastasis 2012; 29:19-25; PMID:21953075; http://dx.doi.org/10.1007/s10585-011-9425-5
14. Sok JC, Coppelli FM, Thomas SM, Lango MN, Xi S, Hunt JL, Freilino ML, Graner MW, Wikstrand CJ, Bigner DD, et al. Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res 2006; 12:5064-73; PMID:16951222; http://dx.doi.org/10.1158/1078-0432.CCR-06-0913 (Pubitemid 44453332)
15. Mukherjee B, McEllin B, Camacho CV, Tomimatsu N, Sirasanagandala S, Nannepaga S, Hatanpaa KJ, Mickey B, Madden C, Maher E, et al. EGFRvIII and DNA double-strand break repair: a molecular mechanism for radioresistance in glioblastoma. Cancer Res 2009; 69:4252-9; PMID:19435898; http://dx.doi.org/10. 1158/0008-5472.CAN-08-4853
16. Tinhofer I, Klinghammer K, Weichert W, Knödler M, Stenzinger A, Gauler T, Budach V, Keilholz U. Expression of amphiregulin and EGFRvIII affect outcome of patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment. Clin Cancer Res 2011; 17:5197-204; PMID:21653686; http://dx.doi.org/10.1158/1078-0432.CCR-10-3338
17. Hoa M, Davis SL, Ames SJ, Spanjaard RA. Amplification of wild-type K-ras promotes growth of head and neck squamous cell carcinoma. Cancer Res 2002; 62:7154-6; PMID:12499248 (Pubitemid 36025228)
18. Murugan AK, Hong NT, Fukui Y, Munirajan AK, Tsuchida N. Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas. Int J Oncol 2008; 32:101-11; PMID:18097548 (Pubitemid 351176067)
19. Toulany M, Baumann M, Rodemann HP. Stimulated PI3K-AKT signaling mediated through ligand or radiation-induced EGFR depends indirectly, but not directly, on constitutive K-Ras activity. Mol Cancer Res 2007; 5:863-72; PMID:17699110; http://dx.doi.org/10.1158/1541-7786.MCR-06-0297 (Pubitemid 47294813)
20. Minjgee M, Toulany M, Kehlbach R, Giehl K, Rodemann HPK-RAS. K-RAS(V12) induces autocrine production of EGFR ligands and mediates radioresistance through EGFR-dependent Akt signaling and activation of DNA-PKcs. Int J Radiat Oncol Biol Phys 2011; 81:1506-14; PMID:21985943; http://dx.doi.org/10.1016/j. ijrobp.2011.05.057
21. Sunayama J, Matsuda K, Sato A, Tachibana K, Suzuki K, Narita Y, Shibui S, Sakurada K, Kayama T, Tomiyama A, et al. Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells. Stem Cells 2010; 28:1930-9; PMID:20857497; http://dx.doi.org/10.1002/stem.521
22. Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007; 7:169-81; PMID:17318210; http://dx.doi.org/10.1038/nrc2088
23. Soria JC, Mok TS, Cappuzzo F, Jänne PA. EGFRmutated oncogene-addicted non-small cell lung cancer: current trends and future prospects. Cancer Treat Rev 2012; 38:416-30; PMID:22119437; http://dx.doi.org/ 10.1016/j.ctrv.2011.10.003
24. He C, Liu M, Zhou C, Zhang J, Ouyang M, Zhong N, Xu J. Detection of epidermal growth factor receptor mutations in plasma by mutant-enriched PCR assay for prediction of the response to gefitinib in patients with non-small-cell lung cancer. Int J Cancer 2009; 125:2393-9; PMID:19530244; http://dx.doi.org/10.1002/ijc.24653
25. Mack PC, Holland WS, Burich RA, Sangha R, Solis LJ, Li Y, Beckett LA, Lara PN Jr., Davies AM, Gandara DR. EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer. J Thorac Oncol 2009; 4:1466-72; PMID:19884861; http://dx.doi.org/10.1097/JTO.0b013e3181bbf239
26. Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG, Varmus HE. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005; 2:e17; PMID:15696205; http://dx.doi.org/10.1371/journal.pmed.0020017
27. Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, Bekele BN, Herbst RS, Wistuba II. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res 2007; 13:2890-6; PMID:17504988; http://dx.doi.org/10.1158/1078-0432.CCR-06-3043 (Pubitemid 46849563)
28. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009; 27:2091-6; PMID:19188670; http://dx.doi.org/10.1200/JCO.2009.21.9170
29. Sunaga N, Shames DS, Girard L, Peyton M, Larsen JE, Imai H, Soh J, Sato M, Yanagitani N, Kaira K, et al. Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy. Mol Cancer Ther 2011; 10:336-46; PMID:21306997; http://dx.doi.org/10. 1158/1535-7163.MCT-10-0750
30. Saki M, Toulany M, Rodemann HP. Acquired resistance to cetuximab is associated with the overexpression of Ras family members and the loss of radiosensitization in head and neck cancer cells. Radiother Oncol 2013; 108:473-8; PMID:23891090; http://dx.doi.org/10.1016/j.radonc.2013.06.023
31. Cengel KA, Voong KR, Chandrasekaran S, Maggiorella L, Brunner TB, Stanbridge E, Kao GD, McKenna WG, Bernhard EJ. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells. Neoplasia 2007; 9:341-8; PMID:17460778; http://dx.doi.org/10.1593/neo.06823 (Pubitemid 46608301)
32. Gupta S, Ramjaun AR, Haiko P, Wang Y, Warne PH, Nicke B, Nye E, Stamp G, Alitalo K, Downward J. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell 2007; 129:957-68; PMID:17540175; http://dx.doi.org/10.1016/j.cell.2007.03.051 (Pubitemid 46802703)
33. Ciuffreda L, Di Sanza C, Cesta Incani U, Eramo A, Desideri M, Biagioni F, Passeri D, Falcone I, Sette G, Bergamo P, et al. The mitogen-activated protein kinase (MAPK) cascade controls phosphatase and tensin homolog (PTEN) expression through multiple mechanisms. J Mol Med (Berl) 2012; 90:667-79; PMID:22215152; http://dx.doi.org/10.1007/s00109-011-0844-1
34. Zmajkovicova K, Jesenberger V, Catalanotti F, Baumgartner C, Reyes G, Baccarini M. MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance. Mol Cell 2013; 50:43-55; PMID:23453810; http://dx.doi.org/10.1016/j.molcel.2013.01.037
35. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, Markman B, Rodriguez O, Guzman M, Rodriguez S, et al. PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 2011; 30:2547-57; PMID:21278786; http://dx.doi.org/10. 1038/onc.2010.626
36. Toulany M, Schickfluss TA, Eicheler W, Kehlbach R, Schittek B, Rodemann HP. Impact of oncogenic K-RAS on YB-1 phosphorylation induced by ionizing radiation. Breast Cancer Res 2011; 13:R28; PMID:21392397; http://dx.doi.org/10. 1186/bcr2845
37. Eicheler W, Zips D, Dörfler A, Grénman R, Baumann M. Splicing mutations in TP53 in human squamous cell carcinoma lines influence immunohistochemical detection. J Histochem Cytochem 2002; 50:197-204; PMID:11799138; http://dx.doi.org/10.1177/002215540205000207 (Pubitemid 34106758)
38. Bamford S, Dawson E, Forbes S, Clements J, Pettett R, Dogan A, Flanagan A, Teague J, Futreal PA, Stratton MR, et al. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer 2004; 91:355-8; PMID:15188009 (Pubitemid 39037083)
39. Toulany M, Dittmann K, Baumann M, Rodemann HP. Radiosensitization of Ras-mutated human tumor cells in vitro by the specific EGF receptor antagonist BIBX1382BS. Radiother Oncol 2005; 74:117-29; PMID:15734199; http://dx.doi.org/ 10.1016/j. radonc.2004.11.008 (Pubitemid 40331868)