{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:23:32Z","timestamp":1791332612088,"version":"4.3.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"13","license":[{"start":{"date-parts":[[2006,9,25]],"date-time":"2006-09-25T00:00:00Z","timestamp":1159142400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2006,9,25]],"date-time":"2006-09-25T00:00:00Z","timestamp":1159142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2007,3,22]]},"DOI":"10.1038\/sj.onc.1209990","type":"journal-article","created":{"date-parts":[[2006,9,25]],"date-time":"2006-09-25T18:55:36Z","timestamp":1159210536000},"page":"1932-1940","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":655,"title":["Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism"],"prefix":"10.1038","volume":"26","author":[{"given":"X","family":"Wan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Harkavy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Grohar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L J","family":"Helman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,9,25]]},"reference":[{"key":"BF1209990_CR1","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1146\/annurev.immunol.14.1.483","volume":"14","author":"RT Abraham","year":"1996","unstructured":"Abraham RT, Wiederrecht GJ . (1996). Immunopharmacology of rapamycin. Annu Rev Immunol 14: 483\u2013510.","journal-title":"Annu Rev Immunol"},{"key":"BF1209990_CR2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1634\/theoncologist.4-1-34","volume":"4","author":"R Dagher","year":"1999","unstructured":"Dagher R, Helman L . (1999). Rhabdomyosarcoma: an overview. Oncologist 4: 34\u201344.","journal-title":"Oncologist"},{"key":"BF1209990_CR3","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.1038\/sj.onc.1207542","volume":"23","author":"DC Fingar","year":"2004","unstructured":"Fingar DC, Blenis J . (2004). Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23: 3151\u20133171.","journal-title":"Oncogene"},{"key":"BF1209990_CR4","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1101\/gad.995802","volume":"16","author":"DC Fingar","year":"2002","unstructured":"Fingar DC, Salama S, Tsou C, Harlow E, Blenis J . (2002). Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1\/eIF4E. Genes Dev 16: 1472\u20131487.","journal-title":"Genes Dev"},{"key":"BF1209990_CR5","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/ijc.20543","volume":"113","author":"L Goetsch","year":"2005","unstructured":"Goetsch L, Gonzalez A, Leger O, Beck A, Pauwels PJ, Haeuw JF et al. (2005). A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts. Int J Cancer 113: 316\u2013328.","journal-title":"Int J Cancer"},{"key":"BF1209990_CR6","doi-asserted-by":"publisher","first-page":"30958","DOI":"10.1074\/jbc.M202678200","volume":"277","author":"EA Goncharova","year":"2002","unstructured":"Goncharova EA, Goncharov DA, Eszterhas A, Hunter DS, Glassberg MK, Yeung RS et al. (2002). Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem 277: 30958\u201330967.","journal-title":"J Biol Chem"},{"key":"BF1209990_CR7","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1083\/jcb.200403069","volume":"166","author":"LS Harrington","year":"2004","unstructured":"Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H et al. (2004). The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166: 213\u2013223.","journal-title":"J Cell Biol"},{"key":"BF1209990_CR8","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ccr.2005.08.008","volume":"8","author":"N Hay","year":"2005","unstructured":"Hay N . (2005). The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8: 179\u2013183.","journal-title":"Cancer Cell"},{"key":"BF1209990_CR9","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1101\/gad.1212704","volume":"18","author":"N Hay","year":"2004","unstructured":"Hay N, Sonenberg N . (2004). Upstream and downstream of mTOR. Genes Dev 18: 1926\u20131945.","journal-title":"Genes Dev"},{"key":"BF1209990_CR10","doi-asserted-by":"publisher","first-page":"6680","DOI":"10.1038\/sj.onc.1204091","volume":"19","author":"M Hidalgo","year":"2000","unstructured":"Hidalgo M, Rowinsky EK . (2000). The rapamycin-sensitive signal transduction pathway as a target for cancer therapy. Oncogene 19: 6680\u20136686.","journal-title":"Oncogene"},{"key":"BF1209990_CR11","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S1471-4892(03)00071-7","volume":"3","author":"S Huang","year":"2003","unstructured":"Huang S, Houghton PJ . (2003). Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol 3: 371\u2013377.","journal-title":"Curr Opin Pharmacol"},{"key":"BF1209990_CR12","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ncb839","volume":"4","author":"K Inoki","year":"2002","unstructured":"Inoki K, Li Y, Zhu T, Wu J, Guan KL . (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4: 648\u2013657.","journal-title":"Nat Cell Biol"},{"key":"BF1209990_CR13","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1172\/JCI7917","volume":"105","author":"Y Kido","year":"2000","unstructured":"Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, White MF et al. (2000). Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest 105: 199\u2013205.","journal-title":"J Clin Invest"},{"key":"BF1209990_CR14","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1242\/jcs.114.16.2903","volume":"114","author":"MA Lawlor","year":"2001","unstructured":"Lawlor MA, Alessi DR . (2001). PKB\/Akt: a key mediator of cell proliferation, survival and insulin responses? J Cell Sci 114: 2903\u20132910.","journal-title":"J Cell Sci"},{"key":"BF1209990_CR15","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/j.1749-6632.1995.tb26689.x","volume":"766","author":"D LeRoith","year":"1995","unstructured":"LeRoith D, Baserga R, Helman L, Roberts Jr CT . (1995). The role of the insulin-like growth factor-I receptor in cancer. Ann NY Acad Sci 766: 402\u2013408.","journal-title":"Ann NY Acad Sci"},{"key":"BF1209990_CR16","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/S1535-6108(04)00054-6","volume":"5","author":"D LeRoith","year":"2004","unstructured":"LeRoith D, Helman L . (2004). The new kid on the block(ade) of the IGF-1 receptor. Cancer Cell 5: 201\u2013202.","journal-title":"Cancer Cell"},{"key":"BF1209990_CR17","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1083\/jcb.200408161","volume":"167","author":"BD Manning","year":"2004","unstructured":"Manning BD . (2004). Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol 167: 399\u2013403.","journal-title":"J Cell Biol"},{"key":"BF1209990_CR18","doi-asserted-by":"publisher","first-page":"5340","DOI":"10.1038\/sj.onc.1203038","volume":"18","author":"G Merlino","year":"1999","unstructured":"Merlino G, Helman L . (1999). Rhabdomyosarcoma \u2013 working out the pathways. Oncogene 18: 5340\u20135348.","journal-title":"Oncogene"},{"key":"BF1209990_CR19","first-page":"263","volume":"6","author":"CP Minniti","year":"1995","unstructured":"Minniti CP, Luan D, O\u2019Grady C, Rosenfeld RG, Oh Y, Helman LJ . (1995). Insulin-like growth factor II overexpression in myoblasts induces phenotypic changes typical of the malignant phenotype. Cell Growth Differ 6: 263\u2013269.","journal-title":"Cell Growth Differ"},{"key":"BF1209990_CR20","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1158\/0008-5472.CAN-05-2925","volume":"66","author":"KE O\u2019Reilly","year":"2006","unstructured":"O\u2019Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D et al. (2006). mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66: 1500\u20131508.","journal-title":"Cancer Res"},{"key":"BF1209990_CR21","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1200\/JCO.1995.13.8.2123","volume":"13","author":"AS Pappo","year":"1995","unstructured":"Pappo AS, Shapiro DN, Crist WM, Maurer HM . (1995). Biology and therapy of pediatric rhabdomyosarcoma. J Clin Oncol 13: 2123\u20132139.","journal-title":"J Clin Oncol"},{"key":"BF1209990_CR22","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1038\/ncb840","volume":"4","author":"CJ Potter","year":"2002","unstructured":"Potter CJ, Pedraza LG, Xu T . (2002). Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 4: 658\u2013665.","journal-title":"Nat Cell Biol"},{"key":"BF1209990_CR23","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1101\/gad.239102","volume":"16","author":"T Radimerski","year":"2002","unstructured":"Radimerski T, Montagne J, Hemmings-Mieszczak M, Thomas G . (2002). Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6\u2009K signaling. Genes Dev 16: 2627\u20132632.","journal-title":"Genes Dev"},{"key":"BF1209990_CR24","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.cub.2004.06.054","volume":"14","author":"DD Sarbassov","year":"2004","unstructured":"Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H et al. (2004). Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14: 1296\u20131302.","journal-title":"Curr Biol"},{"key":"BF1209990_CR25","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1126\/science.1106148","volume":"307","author":"DD Sarbassov","year":"2005","unstructured":"Sarbassov DD, Guertin DA, Ali SM, Sabatini DM . (2005). Phosphorylation and regulation of Akt\/PKB by the rictor-mTOR complex. Science 307: 1098\u20131101.","journal-title":"Science"},{"key":"BF1209990_CR26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S0092-8674(00)00117-3","volume":"103","author":"T Schmelzle","year":"2000","unstructured":"Schmelzle T, Hall MN . (2000). TOR, a central controller of cell growth. Cell 103: 253\u2013262.","journal-title":"Cell"},{"key":"BF1209990_CR27","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1016\/j.cub.2004.08.026","volume":"14","author":"OJ Shah","year":"2004","unstructured":"Shah OJ, Wang Z, Hunter T . (2004). Inappropriate activation of the TSC\/Rheb\/mTOR\/S6\u2009K cassette induces IRS1\/2 depletion, insulin resistance and cell survival deficiencies. Curr Biol 14: 1650\u20131656.","journal-title":"Curr Biol"},{"key":"BF1209990_CR28","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/ncb995","volume":"5","author":"H Stocker","year":"2004","unstructured":"Stocker H, Radimerski T, Schindelholz B, Wittwer F, Belawat P, Daram P et al. (2004). Rheb is an essential regulator of S6\u2009K in controlling cell growth in Drosophila. Nat Cell Biol 5: 559\u2013565.","journal-title":"Nat Cell Biol"},{"key":"BF1209990_CR29","doi-asserted-by":"publisher","first-page":"7052","DOI":"10.1158\/0008-5472.CAN-05-0917","volume":"65","author":"SY Sun","year":"2005","unstructured":"Sun SY, Rosenberg LM, Wang X, Zhou Z, Yue P, Fu H et al. (2005). Activation of Akt and eIF4E survival pathways by rapamycin-mediated mammalian target of rapamycin inhibition. Cancer Res 65: 7052\u20137058.","journal-title":"Cancer Res"},{"key":"BF1209990_CR30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/352073a0","volume":"352","author":"XJ Sun","year":"1991","unstructured":"Sun XJ, Rothenberg P, Kahn CR, Backer JM, Araki E, Wilden PA et al. (1991). Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 352: 73\u201377.","journal-title":"Nature"},{"key":"BF1209990_CR31","doi-asserted-by":"crossref","first-page":"38052","DOI":"10.1074\/jbc.M106703200","volume":"276","author":"F Tremblay","year":"2001","unstructured":"Tremblay F, Marette A . (2001). Amino acid and insulin signaling via the mTOR\/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells. J Biol Chem 276: 38052\u201338060.","journal-title":"J Biol Chem"},{"key":"BF1209990_CR32","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/sj.neo.7900242","volume":"4","author":"X Wan","year":"2002","unstructured":"Wan X, Helman LJ . (2002). Effect of insulin-like growth factor II on protecting myoblast cells against cisplatin-induced apoptosis through p70 S6 kinase pathway. Neoplasia 4: 400\u2013408.","journal-title":"Neoplasia"},{"key":"BF1209990_CR33","doi-asserted-by":"publisher","first-page":"8205","DOI":"10.1038\/sj.onc.1206878","volume":"22","author":"X Wan","year":"2003","unstructured":"Wan X, Helman LJ . (2003). Levels of PTEN protein modulate Akt phosphorylation on serine 473, but not on threonine 308, in IGF-II-overexpressing rhabdomyosarcomas cells. Oncogene 22: 8205\u20138211.","journal-title":"Oncogene"},{"key":"BF1209990_CR34","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1158\/0008-5472.CAN-04-3135","volume":"65","author":"X Wan","year":"2005","unstructured":"Wan X, Mendoza A, Khanna C, Helman LJ . (2005). Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma. Cancer Res 65: 2406\u20132411.","journal-title":"Cancer Res"},{"key":"BF1209990_CR35","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1023\/A:1006806722619","volume":"182","author":"MF White","year":"1998","unstructured":"White MF . (1998). The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol Cell Biochem 182: 3\u201311.","journal-title":"Mol Cell Biochem"},{"key":"BF1209990_CR36","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1097\/00001622-200007000-00010","volume":"12","author":"RB Womer","year":"2000","unstructured":"Womer RB, Pressey JG . (2000). Rhabdomyosarcoma and soft tissue sarcoma in childhood. Curr Opin Oncol 12: 337\u2013344.","journal-title":"Curr Opin Oncol"},{"key":"BF1209990_CR37","doi-asserted-by":"publisher","first-page":"13118","DOI":"10.1074\/jbc.274.19.13118","volume":"274","author":"L Zhang","year":"1999","unstructured":"Zhang L, Kim M, Choi YH, Goemans B, Yeung C, Hu Z et al. (1999). Diminished G1 checkpoint after gamma-irradiation and altered cell cycle regulation by insulin-like growth factor II overexpression. J Biol Chem 274: 13118\u201313126.","journal-title":"J Biol Chem"}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/1209990.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/1209990","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/1209990.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T09:18:18Z","timestamp":1647940698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/1209990"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,25]]},"references-count":37,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2007,3,22]]}},"alternative-id":["BF1209990"],"URL":"https:\/\/doi.org\/10.1038\/sj.onc.1209990","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,25]]},"assertion":[{"value":"19 May 2006","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2006","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2006","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2006","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}