Inhibition of PI3K/mTOR Leads to Adaptive Resistance in Matrix-Attached Cancer Cells

Cancer Cell

Volumn 21, Issue 2, 2012, Pages 227-239

  Muranen, Taru ^a   Selfors, Laura M ^a   Worster, Devin T ^a   Iwanicki, Marcin P ^a   Song, Loling ^a   Morales, Fabiana C ^b   Gao, Sizhen ^a   Mills, Gordon B ^b   Brugge, Joan S ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; 2 MORPHOLINO 8 PHENYLCHROMONE; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; ANTINEOPLASTIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR; GNE 493; GNE 737; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; N [4 (3 BROMOANILINO) 6 QUINAZOLINYL]ACRYLAMIDE; NAVITOCLAX; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PICTRELISIB; PIK 90; PROTEIN BCL 2; RAPAMYCIN; SOMATOMEDIN C RECEPTOR; TRANSCRIPTION FACTOR FOXO; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BREAST CANCER; CANCER CELL; CANCER INHIBITION; CANCER RESISTANCE; CANCER SURVIVAL; CELL ADHESION; CELL DEATH; CELL SURVIVAL; CELLULAR STRESS RESPONSE; CONTROLLED STUDY; DRUG EFFICACY; FEMALE; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; NUTRIENT SUPPLY; OVARY CANCER; PRIORITY JOURNAL; RNA TRANSLATION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TUMOR SPHEROID; UPREGULATION;

EID: 84856989746     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2011.12.024     Document Type: Article

References (78)

1. Ackler S., Xiao Y., Mitten M.J., Foster K., Oleksijew A., Refici M., Schlessinger S., Wang B., Chemburkar S.R., Bauch J., et al. ABT-263 and rapamycin act cooperatively to kill lymphoma cells invitro and invivo. Mol. Cancer Ther. 2008, 7:3265-3274.
2. Allam H., Ali N. Initiation factor eIF2-independent mode of c-Src mRNA translation occurs via an internal ribosome entry site. J.Biol. Chem. 2010, 285:5713-5725.
3. Baselga J. Targeting the phosphoinositide-3 (PI3) kinase pathway in breast cancer. Oncologist 2011, 16(Suppl. 1):12-19.
4. Braunstein S., Karpisheva K., Pola C., Goldberg J., Hochman T., Yee H., Cangiarella J., Arju R., Formenti S.C., Schneider R.J. A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer. Mol. Cell 2007, 28:501-512.
5. Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., Greenberg M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999, 96:857-868.
6. Carpten J.D., Faber A.L., Horn C., Donoho G.P., Briggs S.L., Robbins C.M., Hostetter G., Boguslawski S., Moses T.Y., Savage S., et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature 2007, 448:439-444.
7. Carracedo A., Ma L., Teruya-Feldstein J., Rojo F., Salmena L., Alimonti A., Egia A., Sasaki A.T., Thomas G., Kozma S.C., et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J.Clin. Invest. 2008, 118:3065-3074.
8. Chandarlapaty S., Sawai A., Scaltriti M., Rodrik-Outmezguine V., Grbovic-Huezo O., Serra V., Majumder P.K., Baselga J., Rosen N. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 2011, 19:58-71.
9. Chiarugi P., Giannoni E. Anoikis: a necessary death program for anchorage-dependent cells. Biochem. Pharmacol. 2008, 76:1352-1364.
10. Choo A.Y., Yoon S.-O., Kim S.G., Roux P.P., Blenis J. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc. Natl. Acad. Sci. USA 2008, 105:17414-17419.
11. Cloughesy T.F., Yoshimoto K., Nghiemphu P., Brown K., Dang J., Zhu S., Hsueh T., Chen Y., Wang W., Youngkin D., et al. Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med. 2008, 5:e8.
12. Courtney K.D., Corcoran R.B., Engelman J.A. The PI3K pathway as drug target in human cancer. J.Clin. Oncol. 2010, 28:1075-1083.
13. Creighton C.J., Massarweh S., Huang S., Tsimelzon A., Hilsenbeck S.G., Osborne C.K., Shou J., Malorni L., Schiff R. Development of resistance to targeted therapies transforms the clinically associated molecular profile subtype of breast tumor xenografts. Cancer Res. 2008, 68:7493-7501.
14. Debnath J., Brugge J.S. Modelling glandular epithelial cancers in three-dimensional cultures. Nat. Rev. Cancer 2005, 5:675-688.
15. Debnath J., Muthuswamy S.K., Brugge J.S. Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 2003, 30:256-268.
16. Debnath J., Walker S.J., Brugge J.S. Akt activation disrupts mammary acinar architecture and enhances proliferation in an mTOR-dependent manner. J.Cell Biol. 2003, 163:315-326.
17. Engelman J.A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 2009, 9:550-562.
18. Engelman J.A., Chen L., Tan X., Crosby K., Guimaraes A.R., Upadhyay R., Maira M., McNamara K., Perera S.A., Song Y., et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med. 2008, 14:1351-1356.
19. Feldman M.E., Apsel B., Uotila A., Loewith R., Knight Z.A., Ruggero D., Shokat K.M. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 2009, 7:e38.
20. Fels D.R., Koumenis C. The PERK/eIF2alpha/ATF4 module of the UPR in hypoxia resistance and tumor growth. Cancer Biol. Ther. 2006, 5:723-728.
21. Fernandez J., Yaman I., Sarnow P., Snider M.D., Hatzoglou M. Regulation of internal ribosomal entry site-mediated translation by phosphorylation of the translation initiation factor eIF2alpha. J.Biol. Chem. 2002, 277:19198-19205.
22. Friedland J.C., Lakins J.N., Kazanietz M.G., Chernoff J., Boettiger D., Weaver V.M. alpha6beta4 integrin activates Rac-dependent p21-activated kinase 1 to drive NF-kappaB-dependent resistance to apoptosis in 3D mammary acini. J.Cell Sci. 2007, 120:3700-3712.
23. Garrett J.T., Olivares M.G., Rinehart C., Granja-Ingram N.D., Sánchez V., Chakrabarty A., Dave B., Cook R.S., Pao W., McKinely E., et al. Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Proc. Natl. Acad. Sci. USA 2011, 108:5021-5026.
24. Gerlitz G., Jagus R., Elroy-Stein O. Phosphorylation of initiation factor-2 alpha is required for activation of internal translation initiation during cell differentiation. Eur. J. Biochem. 2002, 269:2810-2819.
25. Gewinner C., Wang Z.C., Richardson A., Teruya-Feldstein J., Etemadmoghadam D., Bowtell D., Barretina J., Lin W.M., Rameh L., Salmena L., et al. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell 2009, 16:115-125.
26. Gilbert W.V., Zhou K., Butler T.K., Doudna J.A. Cap-independent translation is required for starvation-induced differentiation in yeast. Science 2007, 317:1224-1227.
27. Giménez-Bonafé P., Tortosa A., Pérez-Tomás R. Overcoming drug resistance by enhancing apoptosis of tumor cells. Curr. Cancer Drug Targets 2009, 9:320-340.
28. Guo W., Pylayeva Y., Pepe A., Yoshioka T., Muller W.J., Inghirami G., Giancotti F.G. Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 2006, 126:489-502.
29. Harrington L.S., Findlay G.M., Gray A., Tolkacheva T., Wigfield S., Rebholz H., Barnett J., Leslie N.R., Cheng S., Shepherd P.R., et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J.Cell Biol. 2004, 166:213-223.
30. Hennessy B., Lu Y., Gonzalez-Angulo A.M., Myhre S., Carey M., Ju Z., Coombes K., Liu W., Meric-Bernstam F., Bedrosian I., et al. A technical assessment of the utility of reverse phase protein arrays for the study of the functional proteome in non-microdissested human breast cancer. Clin. Proteomics 2010, 6:129-151.
31. Holcik M., Sonenberg N. Translational control in stress and apoptosis. Nat. Rev. Mol. Cell Biol. 2005, 6:318-327.
32. Holcik M., Lefebvre C., Yeh C., Chow T., Korneluk R.G. A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat. Cell Biol. 1999, 1:190-192.
33. Holcik M., Yeh C., Korneluk R.G., Chow T. Translational upregulation of X-linked inhibitor of apoptosis (XIAP) increases resistance to radiation induced cell death. Oncogene 2000, 19:4174-4177.
34. Howes A.L., Chiang G.G., Lang E.S., Ho C.B., Powis G., Vuori K., Abraham R.T. The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures. Mol. Cancer Ther. 2007, 6:2505-2514.
35. Hsieh A.C., Costa M., Zollo O., Davis C., Feldman M.E., Testa J.R., Meyuhas O., Shokat K.M., Ruggero D. Genetic dissection of the oncogenic mTOR pathway reveals druggable addiction to translational control via 4EBP-eIF4E. Cancer Cell 2010, 17:249-261.
36. Isakoff S.J., Engelman J.A., Irie H.Y., Luo J., Brachmann S.M., Pearline R.V., Cantley L.C., Brugge J.S. Breast cancer-associated PIK3CA mutations are oncogenic in mammary epithelial cells. Cancer Res. 2005, 65:10992-11000.
37. Jain H.V., Meyer-Hermann M. The molecular basis of synergism between carboplatin and ABT-737 therapy targeting ovarian carcinomas. Cancer Res. 2011, 71:705-715.
38. Jefferson L.S., Kimball S.R. Amino acids as regulators of gene expression at the level of mRNA translation. J.Nutr. 2003, 133(6, Suppl 1):2046S-2051S.
39. Johannes G., Carter M.S., Eisen M.B., Brown P.O., Sarnow P. Identification of eukaryotic mRNAs that are translated at reduced cap binding complex eIF4F concentrations using a cDNA microarray. Proc. Natl. Acad. Sci. USA 1999, 96:13118-13123.
40. Kenny P.A., Lee G.Y., Myers C.A., Neve R.M., Semeiks J.R., Spellman P.T., Lorenz K., Lee E.H., Barcellos-Hoff M.H., Petersen O.W., et al. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol. Oncol. 2007, 1:84-96.
41. Kops G.J., de Ruiter N.D., De Vries-Smits A.M., Powell D.R., Bos J.L., Burgering B.M. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 1999, 398:630-634.
42. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943-1947.
43. Liu H., Radisky D.C., Wang F., Bissell M.J. Polarity and proliferation are controlled by distinct signaling pathways downstream of PI3-kinase in breast epithelial tumor cells. J.Cell Biol. 2004, 164:603-612.
44. Maira S.M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., Brachmann S., Chène P., De Pover A., Schoemaker K., et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent invivo antitumor activity. Mol. Cancer Ther. 2008, 7:1851-1863.
45. Marr M.T., D'Alessio J.A., Puig O., Tjian R. IRES-mediated functional coupling of transcription and translation amplifies insulin receptor feedback. Genes Dev. 2007, 21:175-183.
46. Martin M.J., Melnyk N., Pollard M., Bowden M., Leong H., Podor T.J., Gleave M., Sorensen P.H. The insulin-like growth factor I receptor is required for Akt activation and suppression of anoikis in cells transformed by the ETV6-NTRK3 chimeric tyrosine kinase. Mol. Cell. Biol. 2006, 26:1754-1769.
47. Massarweh S., Osborne C.K., Creighton C.J., Qin L., Tsimelzon A., Huang S., Weiss H., Rimawi M., Schiff R. Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res. 2008, 68:826-833.
48. Moerke N.J., Aktas H., Chen H., Cantel S., Reibarkh M.Y., Fahmy A., Gross J.D., Degterev A., Yuan J., Chorev M., et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell 2007, 128:257-267.
49. Muaddi H., Majumder M., Peidis P., Papadakis A.I., Holcik M., Scheuner D., Kaufman R.J., Hatzoglou M., Koromilas A.E. Phosphorylation of eIF2α at serine 51 is an important determinant of cell survival and adaptation to glucose deficiency. Mol. Biol. Cell 2010, 21:3220-3231.
50. O'Reilly K.E., Rojo F., She Q.-B., Solit D., Mills G.B., Smith D., Lane H., Hofmann F., Hicklin D.J., Ludwig D.L., et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006, 66:1500-1508.
51. Oltersdorf T., Elmore S.W., Shoemaker A.R., Armstrong R.C., Augeri D.J., Belli B.A., Bruncko M., Deckwerth T.L., Dinges J., Hajduk P.J., et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005, 435:677-681.
52. Plati J., Bucur O., Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr. Biol. (Camb.) 2011, 3:279-296.
53. Polo M.L., Arnoni M.V., Riggio M., Wargon V., Lanari C., Novaro V. Responsiveness to PI3K and MEK inhibitors in breast cancer. Use of a 3D culture system to study pathways related to hormone independence in mice. PLoS ONE 2010, 5:e10786.
54. Puig O., Tjian R. Transcriptional feedback control of insulin receptor by dFOXO/FOXO1. Genes Dev. 2005, 19:2435-2446.
55. Raven J.F., Koromilas A.E. PERK and PKR: old kinases learn new tricks. Cell Cycle 2008, 7:1146-1150.
56. Riggins R.B., Schrecengost R.S., Guerrero M.S., Bouton A.H. Pathways to tamoxifen resistance. Cancer Lett. 2007, 256:1-24.
57. Samuels Y., Velculescu V.E. Oncogenic mutations of PIK3CA in human cancers. Cell Cycle 2004, 3:1221-1224.
58. Samuels Y., Wang Z., Bardelli A., Silliman N., Ptak J., Szabo S., Yan H., Gazdar A., Powell S.M., Riggins G.J., et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004, 304:554.
59. Schafer Z.T., Grassian A.R., Song L., Jiang Z., Gerhart-Hines Z., Irie H.Y., Gao S., Puigserver P., Brugge J.S. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009, 461:109-113.
60. Sengupta S., Peterson T.R., Sabatini D.M. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol. Cell 2010, 40:310-322.
61. Sergina N.V., Rausch M., Wang D., Blair J., Hann B., Shokat K.M., Moasser M.M. Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive HER3. Nature 2007, 445:437-441.
62. Serra V., Scaltriti M., Prudkin L., Eichhorn P.J.A., Ibrahim Y.H., 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, 30:2547-2557.
63. She Q.-B., Halilovic E., Ye Q., Zhen W., Shirasawa S., Sasazuki T., Solit D.B., Rosen N. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 2010, 18:39-51.
64. Silvera D., Formenti S.C., Schneider R.J. Translational control in cancer. Nat. Rev. Cancer 2010, 10:254-266.
65. Suo J., Snider S.J., Mills G.B., Creighton C.J., Chen A.C., Schiff R., Lloyd R.E., Chang E.C. Int6 regulates both proteasomal degradation and translation initiation and is critical for proper formation of acini by human mammary epithelium. Oncogene 2010, 30:724-736.
66. Sutherlin D.P., Sampath D., Berry M., Castanedo G., Chang Z., Chuckowree I., Dotson J., Folkes A., Friedman L., Goldsmith R., et al. Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer. J.Med. Chem. 2010, 53:1086-1097.
67. Syntichaki P., Troulinaki K., Tavernarakis N. eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 2007, 445:922-926.
68. Terenin I.M., Dmitriev S.E., Andreev D.E., Shatsky I.N. Eukaryotic translation initiation machinery can operate in a bacterial-like mode without eIF2. Nat. Struct. Mol. Biol. 2008, 15:836-841.
69. Thoreen C.C., Kang S.A., Chang J.W., Liu Q., Zhang J., Gao Y., Reichling L.J., Sim T., Sabatini D.M., Gray N.S. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J.Biol. Chem. 2009, 284:8023-8032.
70. Villa-Cuesta E., Sage B.T., Tatar M. A role for Drosophila dFoxO and dFoxO 5'UTR internal ribosomal entry sites during fasting. PLoS ONE 2010, 5:e11521.
71. Walensky L.D. BCL-2 in the crosshairs: tipping the balance of life and death. Cell Death Differ. 2006, 13:1339-1350.
72. Weaver V.M., Lelièvre S., Lakins J.N., Chrenek M.A., Jones J.C.R., Giancotti F., Werb Z., Bissell M.J. beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2002, 2:205-216.
73. Weigelt B., Bissell M.J. Unraveling the microenvironmental influences on the normal mammary gland and breast cancer. Semin. Cancer Biol. 2008, 18:311-321.
74. Weigelt B., Lo A.T., Park C.C., Gray J.W., Bissell M.J. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment. Breast Cancer Res. Treat. 2010, 122:35-43.
75. Wek R.C., Jiang H.-Y., Anthony T.G. Coping with stress: eIF2 kinases and translational control. Biochem. Soc. Trans. 2006, 34:7-11.
76. Yamada K.M., Cukierman E. Modeling tissue morphogenesis andcancer in 3D. Cell 2007, 130:601-610.
77. Yamaguchi S., Ishihara H., Yamada T., Tamura A., Usui M., Tominaga R., Munakata Y., Satake C., Katagiri H., Tashiro F., et al. ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell Metab. 2008, 7:269-276.
78. Yuan T.L., Cantley L.C. PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008, 27:5497-5510.