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Akt-dependent transformation: there is more to growth than just surviving

Oncogene volume 24, pages 7435–7442 (2005)Cite this article

Abstract

Activation of the Akt/PKB protein kinase family triggers increases in cell size, metabolism and survival. Akt coordinately regulates these fundamental cellular processes through phosphorylation-dependent inactivation of tumor suppressors and activation of trophic signaling. Akt signaling stimulates transport and metabolism of both glucose and amino acids, which in turn support mTOR-dependent increases in protein translation. In addition, Akt activation directs cells to undertake a metabolic conversion from oxidative phosphorylation to aerobic glycolysis. Although this conversion promotes cell growth, it also renders cell survival dependent on a continuous supply of extracellular nutrients, which themselves are required regulatory elements in Akt signal transduction.

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References

  • Alessi DR, Deak M, Casamayor A, Caudwell FB, Morrice N, Norman DG, Gaffney P, Reese CB, MacDougall CN, Harbison D, Ashworth A and Bownes M . (1997). Curr. Biol., 7, 776–789.

  • Arsham AM, Plas DR, Thompson CB and Simon MC . (2002). J. Biol. Chem., 277, 15162–15170.

  • Bae SS, Cho H, Mu J and Birnbaum MJ . (2003). J. Biol. Chem., 278, 49530–49536.

  • Barnes D and Colowick SP . (1976). J. Cell Physiol., 89, 633–639.

  • Barnes K, McIntosh E, Whetton AD, Daley GQ, Bentley J and Baldwin SA . (2005). Oncogene, 24, 3257–3267.

  • Bauer DE, Harris MH, Plas DR, Lum JJ, Hammerman PS, Rathmell JC, Riley JL and Thompson CB . (2004). FASEB J., 18, 1303–1305.

  • Bauer DE, Hatzivassiliou G, Zhao F, Andreadis C and Thompson CB . Oncogene (in press).

  • Berwick DC, Hers I, Heesom KJ, Moule SK and Tavare JM . (2002). J. Biol. Chem., 277, 33895–33900.

  • Boerner P, Resnick RJ and Racker E . (1985). Proc. Natl. Acad. Sci. USA, 82, 1350–1353.

  • Brazil DP, Yang ZZ and Hemmings BA . (2004). Trends Biochem. Sci., 29, 233–242.

  • Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW and Kaelin Jr WG . (2004). Genes Dev., 18, 2893–2904.

  • Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J and Greenberg ME . (1999). Cell, 96, 857–868.

  • Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW and Greenberg ME . (2004). Science, 303, 2011–2015.

  • Burgering BM and Coffer PJ . (1995). Nature, 376, 599–602.

  • Burgering BM and Kops GJ . (2002). Trends Biochem Sci., 27, 352–360.

  • Buzzai M, Bauer DE, Jones RG, Deberardinis RJ, Hatzivassiliou G, Elstrom RL and Thompson CB . (2005). Oncogene, 24, 4165–4173.

  • Calera MR, Martinez C, Liu H, Jack AK, Birnbaum MJ and Pilch PF . (1998). J. Biol. Chem., 273, 7201–7204.

  • Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw III EB, Kaestner KH, Bartolomei MS, Shulman GI and Birnbaum MJ . (2001). Science, 292, 1728–1731.

  • Corradetti MN, Inoki K, Bardeesy N, DePinho RA and Guan KL . (2004). Genes Dev., 18, 1533–1538.

  • Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, Nakajima T and Fukamizu A . (2004). Proc. Natl. Acad. Sci. USA, 101, 10042–10047.

  • Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Yeung RS, Halley DJ, Nicosia SV, Pledger WJ and Cheng JQ . (2002). J. Biol. Chem., 11, 11.

  • Dennis PB, Fumagalli S and Thomas G . (1999). Curr. Opin. Genet. Dev., 9, 49–54.

  • Dennis PB, Jaeschke A, Saitoh M, Fowler B, Kozma SC and Thomas G . (2001). Science, 294, 1102–1105.

  • Dowell P, Otto TC, Adi S and Lane MD . (2003). J. Biol. Chem., 278, 45485–45491.

  • Edinger AL, Linardic CM, Chiang GG, Thompson CB and Abraham RT . (2003). Cancer Res., 63, 8451–8460.

  • Edinger AL and Thompson CB . (2002). Mol. Biol. Cell., 13, 2276–2288.

  • Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM and Thompson CB . (2004). Cancer Res., 64, 3892–3899.

  • Fingar DC, Hausdorff SF, Blenis J and Birnbaum MJ . (1993). J. Biol. Chem., 268, 3005–3008.

  • Frescas D, Valenti L and Accili D . (2005). J. Biol. Chem., 280, 20589–20595.

  • Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung RS, Ru B and Pan D . (2002). Nat. Cell. Biol., 4, 699–704.

  • Garami A, Zwartkruis FJ, Nobukuni T, Joaquin M, Roccio M, Stocker H, Kozma SC, Hafen E, Bos JL and Thomas G . (2003). Mol. Cell, 11, 1457–1466.

  • Garofalo RS, Orena SJ, Rafidi K, Torchia AJ, Stock JL, Hildebrandt AL, Coskran T, Black SC, Brees DJ, Wicks JR, McNeish JD and Coleman KG . (2003). J. Clin. Invest., 112, 197–208.

  • Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB and Hay N . (2001). Genes Dev., 15, 1406–1418.

  • Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C and Avruch J . (1998). J. Biol. Chem., 273, 14484–14494.

  • Hardwick JS, Kuruvilla FG, Tong JK, Shamji AF and Schreiber SL . (1999). Proc. Natl. Acad. Sci. USA, 96, 14866–14870.

  • Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, Barnett J, Leslie NR, Cheng S, Shepherd PR, Gout I, Downes CP and Lamb RF . (2004). J. Cell. Biol., 166, 213–223.

  • Harris MH, Vander Heiden MG, Kron SJ and Thompson CB . (2000). Mol. Cell. Biol., 20, 3590–3596.

  • Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, Alessi DR and Hardie DG . (2003). J. Biol., 2, 28.

  • Hay N and Sonenberg N . (2004). Genes Dev., 18, 1926–1945.

  • Hong SP, Leiper FC, Woods A, Carling D and Carlson M . (2003). Proc. Natl. Acad. Sci. USA, 100, 8839–8843.

  • Hosaka T, Biggs III WH, Tieu D, Boyer AD, Varki NM, Cavenee WK and Arden KC . (2004). Proc. Natl. Acad. Sci. USA, 101, 2975–2980.

  • Huang H, Regan KM, Wang F, Wang D, Smith DI, van Deursen JM and Tindall DJ . (2005). Proc. Natl. Acad. Sci. USA, 102, 1649–1654.

  • Hyde R, Taylor PM and Hundal HS . (2003). Biochem. J., 373, 1–18.

  • Inoki K, Li Y, Xu T and Guan KL . (2003a). Genes Dev., 17, 1829–1834.

  • Inoki K, Li Y, Zhu T, Wu J and Guan KL . (2002). Nat. Cell. Biol., 4, 648–657.

  • Inoki K, Zhu T and Guan KL . (2003b). Cell, 115, 577–590.

  • Jacobs FM, van der Heide LP, Wijchers PJ, Burbach JP, Hoekman MF and Smidt MP . (2003). J. Biol. Chem., 278, 35959–35967.

  • Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ and Thompson CB . (2005). Mol. Cell, 18, 283–293.

  • Kaestner KH, Knochel W and Martinez DE . (2000). Genes Dev., 14, 142–146.

  • Kim JW, Zeller KI, Wang Y, Jegga AG, Aronow BJ, O'Donnell KA and Dang CV . (2004). Mol. Cell. Biol., 24, 5923–5936.

  • Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH and Burgering BM . (2002). Nature, 419, 316–321.

  • Lee SS, Kennedy S, Tolonen AC and Ruvkun G . (2003). Science, 300, 644–647.

  • Mackenzie B and Erickson JD . (2004). Pflugers. Arch., 447, 784–795.

  • Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB and Hay N . (2004). Mol. Cell, 16, 819–830.

  • Manning BD . (2004). J. Cell. Biol., 167, 399–403.

  • Manning BD, Tee AR, Logsdon MN, Blenis J and Cantley LC . (2002). Mol. Cell, 10, 151–162.

  • McElwee J, Bubb K and Thomas JH . (2003). Aging Cell, 2, 111–121.

  • Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M and Guarente L . (2004). Cell, 116, 551–563.

  • Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H and Kenyon C . (2003). Nature, 424, 277–283.

  • Nemoto S, Fergusson MM and Finkel T . (2005). J. Biol. Chem., 280, 16456–16460.

  • Nemoto S and Finkel T . (2002). Science, 295, 2450–2452.

  • Patel J, McLeod LE, Vries RG, Flynn A, Wang X and Proud CG . (2002). Eur. J. Biochem., 269, 3076–3085.

  • Peng T, Golub TR and Sabatini DM . (2002). Mol. Cell. Biol., 22, 5575–5584.

  • Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG and Hay N . (2003). Genes Dev., 17, 1352–1365.

  • Plas DR, Talapatra S, Edinger AL, Rathmell JC and Thompson CB . (2001). J. Biol. Chem., 276, 12041–12048.

  • Plas DR and Thompson CB . (2003). J. Biol. Chem., 278, 12361–12366.

  • Potter CJ, Pedraza LG and Xu T . (2002). Nat. Cell. Biol., 4, 658–665.

  • Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D and Spiegelman BM . (2003). Nature, 423, 550–555.

  • Radimerski T, Montagne J, Hemmings-Mieszczak M and Thomas G . (2002). Genes Dev., 16, 2627–2632.

  • Ramanathan A, Wang C and Schreiber SL . (2005). Proc. Natl. Acad. Sci. USA, 102, 5992–5997.

  • Ramaswamy S, Nakamura N, Sansal I, Bergeron L and Sellers WR . (2002). Cancer Cell, 2, 81–91.

  • Rathmell JC, Farkash EA, Gao W and Thompson CB . (2001). J. Immunol., 167, 6869–6876.

  • Rathmell JC, Fox CJ, Plas DR, Hammerman PS, Cinalli RM and Thompson CB . (2003). Mol. Cell. Biol., 23, 7315–7328.

  • Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA and Thompson CB . (2000). Mol. Cell, 6, 683–692.

  • Reiling JH and Hafen E . (2004). Genes Dev., 18, 2879–2892.

  • Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM and Puigserver P . (2005). Nature, 434, 113–118.

  • Saltiel AR and Kahn CR . (2001). Nature, 414, 799–806.

  • Sarbassov DD, Guertin DA, Ali SM and Sabatini DM . (2005). Science, 307, 1098–1101.

  • Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D and Edgar BA . (2003). Nat. Cell. Biol., 5, 566–571.

  • Schmelzle T and Hall MN . (2000). Cell, 103, 253–262.

  • Schmidt A, Beck T, Koller A, Kunz J and Hall MN . (1998). EMBO J., 17, 6924–6931.

  • Shoshani T, Faerman A, Mett I, Zelin E, Tenne T, Gorodin S, Moshel Y, Elbaz S, Budanov A, Chajut A, Kalinski H, Kamer I, Rozen A, Mor O, Keshet E, Leshkowitz D, Einat P, Skaliter R and Feinstein E . (2002). Mol. Cell. Biol., 22, 2283–2293.

  • Smith EM, Finn SG, Tee AR, Browne GJ and Proud CG . (2005). J. Biol. Chem., 280, 18717–18727.

  • Sofer A, Lei K, Johannessen CM and Ellisen LW . (2005). Mol. Cell. Biol., 25, 5834–5845.

  • Tee AR, Manning BD, Roux PP, Cantley LC and Blenis J . (2003). Curr. Biol., 13, 1259–1268.

  • Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J and Thomas G . (2004). Nature, 431, 200–205.

  • van der Heide LP, Jacobs FM, Burbach JP, Hoekman MM and Smidt MP . (2005). Biochem. J. (in press).

  • van der Horst A, Tertoolen LG, de Vries-Smits LM, Frye RA, Medema RH and Burgering BM . (2004). J. Biol. Chem., 279, 28873–28879.

  • Vander Heiden MG, Plas DR, Rathmell JC, Fox CJ, Harris MH and Thompson CB . (2001). Mol. Cell. Biol., 21, 5899–5912.

  • Wang X, Campbell LE, Miller CM and Proud CG . (1998). Biochem. J., 334 (Part 1), 261–267.

  • West MJ, Stoneley M and Willis AE . (1998). Oncogene, 17, 769–780.

  • Whetton AD, Bazill GW and Dexter TM . (1984). EMBO J., 3, 409–413.

  • Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M and Carling D . (2003). Curr. Biol., 13, 2004–2008.

  • Yamada E, Okada S, Saito T, Ohshima K, Sato M, Tsuchiya T, Uehara Y, Shimizu H and Mori M . (2005). J. Cell. Biol., 168, 921–928.

  • Yang Y, Hou H, Haller EM, Nicosia SV and Bai W . (2005). EMBO J., 24, 1021–1032.

  • Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA and Pan D . (2003). Nat. Cell. Biol., 5, 578–581.

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Acknowledgements

We thank Dr Pat Dennis (University of Cincinnati) and Dr Kim Rathmell (University of North Carolina) for critical reading and discussion of the manuscript.

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  1. Department of Genome Science, The Genome Research Institute, University of Cincinnati, 2180 E. Galbraith Road, Cincinnati, 45237, OH, USA

    David R Plas

  2. Department of Cancer Biology, The Abramson Cancer Research Institute, University of Pennsylvania, 421 Curie Blvd., Philadelphia, 19146, PA, USA

    Craig B Thompson

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Correspondence to David R Plas.

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Plas, D., Thompson, C. Akt-dependent transformation: there is more to growth than just surviving. Oncogene 24, 7435–7442 (2005). https://doi.org/10.1038/sj.onc.1209097

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