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Multiple cell death pathways as regulators of tumour initiation and progression

Abstract

Acquired defects in signalling pathways leading to programmed cell death (PCD) are among the major hallmarks of cancer. Although focus has been on caspase-dependent apoptotic death pathways, evidence is now accumulating that nonapoptotic PCD also can form an important barrier against tumour initiation and progression. Akin to the earlier landmark discoveries that lead to the identification of the major cancer-related proteins like p53, c-Myc and Bcl-2 as controllers of spontaneous and therapy-induced apoptosis, numerous proteins with properties of tumour suppressors and oncoproteins have recently been identified as key regulators of alternative death programmes. The emerging data on the molecular mechanisms regulating nonapoptotic PCD may have potent therapeutic consequences.

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References

  • Alexander CM, Howard EW, Bissell MJ and Werb Z . (1996). J. Cell Biol., 135, 1669–1677.

  • Alonso M, Tamasdan C, Miller DC and Newcomb EW . (2003). Mol. Cancer Ther., 2, 139–150.

  • Altairac S, Zeggai S, Perani P, Courtois Y and Torriglia A . (2003). Cell Death Differ., 10, 548–557.

  • Arico S, Petiot A, Bauvy C, Dubbelhuis PF, Meijer AJ, Codogno P and Ogier-Denis E . (2001). J. Biol. Chem., 276, 35243–35246.

  • Ashkenazi A . (2002). Nat. Rev. Cancer, 2, 420–430.

  • Bao JJ, Le XF, Wang RY, Yuan J, Wang L, Atkinson EN, LaPushin R, Andreeff M, Fang B, Yu Y and Bast Jr RC . (2002). Cancer Res., 62, 7264–7272.

  • Bidere N, Lorenzo HK, Carmona S, Laforge M, Harper F, Dumont C and Senik A . (2003). J. Biol. Chem., 278, 31401–31411.

  • Boya P, Andreau K, Poncet D, Zamzami N, Perfettini JL, Metivier D, Ojcius DM, Jäättelä M and Kroemer G . (2003). J. Exp. Med., 197, 1323–1334.

  • Brunk UT, Neuzil J and Eaton JW . (2001). Redox Rep., 6, 91–97.

  • Brunk UT and Svensson I . (1999). Redox Rep., 4, 3–11.

  • Bursch W, Ellinger A, Kienzl H, Torok L, Pandey S, Sikorska M, Walker R and Hermann RS . (1996). Carcinogenesis, 17, 1595–1607.

  • Chan HT, Hughes D, French RR, Tutt AL, Walshe CA, Teeling JL, Glennie MJ and Cragg MS . (2003). Cancer Res., 63, 5480–5489.

  • Charette SJ, Lambert H and Landry J . (2001). J. Biol. Chem., 276, 36071–36074.

  • Chen G, Shu J and Stacey DW . (1997). Oncogene, 15, 1643–1651.

  • Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S and Kuchino Y . (1999). Oncogene, 18, 2281–2290.

  • Choi WS, Lee EH, Chung CW, Jung YK, Jin BK, Kim SU, Oh TH, Saido TC and Oh YJ . (2001). J. Neurochem., 77, 1531–1541.

  • Cirman T, Oresic K, Droga Mazovec G, Turk V, Reed JC, Myers RM, Salvesen GS and Turk B . (2003). J. Biol. Chem.,,published online October 27.

  • Coultas L and Strasser A . (2003). Semin. Cancer Biol., 13, 115–123.

  • Creagh EM, Carmody RJ and Cotter TG . (2000). Exp. Cell Res., 257, 58–66.

  • Downward J . (2003). Nat. Rev. Cancer, 3, 11–22.

  • Du C, Fang M, Li Y, Li L and Wang X . (2000). Cell, 102, 33–42.

  • Duffy MJ . (1996). Clin. Cancer Res., 2, 613–618.

  • Elliott K, Ge K, Du W and Prendergast GC . (2000). Oncogene, 19, 4669–4684.

  • Evan GI and Vousden KH . (2001). Nature, 411, 342–348.

  • Evan GI, Wyllie AH, Gilbert CS, Littlewood TD, Land H, Brooks M, Waters CM, Penn LZ and Hancock DC . (1992). Cell, 69, 119–128.

  • Ferri KR and Kroemer G . (2001). Nat. Cell Biol., 3, E255–E263.

  • Foghsgaard L, Lademann U, Wissing D, Poulsen B and Jäättelä M . (2002). J. Biol. Chem., 277, 39499–39506.

  • Foghsgaard L, Wissing D, Mauch D, Lademann U, Bastholm L, Boes M, Elling F, Leist M and Jäättelä M . (2001). J. Cell Biol., 153, 999–1009.

  • Forcet C, Ye X, Granger L, Corset V, Shin H, Bredesen DE and Mehlen P . (2001). Proc. Natl. Acad. Sci. USA, 98, 3416–3421.

  • Frese S, Schaper M, Kuster JR, Miescher D, Jäättelä M, Buehler T and Schmid RA . (2003). J. Thorac. Cardiovasc. Surg., 126, 748–754.

  • Frisch SM and Francis H . (1994). J. Cell Biol., 124, 619–626.

  • Gong JG, Costanzo A, Yang HQ, Melino G, Kaelin Jr WG, Levrero M and Wang JY . (1999). Nature, 399, 806–809.

  • Hanahan D and Weinberg RA . (2000). Cell, 100, 57–70.

  • Harkin DP, Bean JM, Miklos D, Song YH, Truong VB, Englert C, Christians FC, Ellisen LW, Maheswaran S, Oliner JD and Haber DA . (1999). Cell, 97, 575–586.

  • Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B and Tschopp J . (2000). Nat. Immunol., 1, 489–495.

  • Inbal B, Bialik S, Sabanay I, Shani G and Kimchi A . (2002). J. Cell Biol., 157, 455–468.

  • Jäättelä M . (1999). Exp. Cell Res., 248, 30–43.

  • Jäättelä M and Tschopp J . (2003). Nat. Immunol., 4, 416–423.

  • Jin Y and Gallagher PJ . (2003). J. Biol. Chem., published online October 6.

  • Joseph B, Marchetti P, Formstecher P, Kroemer G, Lewensohn R and Zhivotovsky B . (2002). Oncogene, 21, 65–77.

  • Kaufmann SH and Hengartner MO . (2001). Trends Cell Biol., 11, 526–534.

  • Kelliher MA, Grimm S, Ishida Y, Kuo F, Stanger BZ and Leder P . (1998). Immunity, 8, 297–303.

  • Kennedy NJ, Sluss HK, Jones SN, Bar-Sagi D, Flavell RA and Davis RJ . (2003). Genes Dev., 17, 629–637.

  • Kerr JFR, Wyllie AH and Currie AR . (1972). Br. J. Cancer, 26, 239–257.

  • Khwaja A and Tatton L . (1999). J. Biol. Chem., 274, 36817–36823.

  • Kinoshita T, Shirouzu M, Kamiya A, Hashimoto K, Yokoyama S and Miyajima A . (1997). Oncogene, 15, 619–627.

  • Komata T, Kanzawa T, Takeuchi H, Germano IM, Schreiber M, Kondo Y and Kondo S . (2003). Br. J. Cancer, 88, 1277–1280.

  • Kothari S, Cizeau J, McMillan-Ward E, Israels SJ, Bailes M, Ens K, Kirshenbaum LA and Gibson SB . (2003). Oncogene, 22, 4734–4744.

  • Kubasiak LA, Hernandez OM, Bishopric NH and Webster KA . (2002). Proc. Natl. Acad. Sci. USA, 99, 12825–12830.

  • Kuopio T, Kankaanranta A, Jalava P, Kronqvist P, Kotkansalo T, Weber E and Collan Y . (1998). Cancer Res., 58, 432–436.

  • Lam M, Dubyak G, Chen L, Nuñez G, Miesfeld RL and Distelhorst CW . (1994). Proc. Natl. Acad. Sci. USA, 91, 6569–6573.

  • Lamy L, Ticchioni M, Rouquette-Jazdanian AK, Samson M, Deckert M, Greenberg AH and Bernard A . (2003). J. Biol. Chem., 278, 23915–23921.

  • Lassus P, Opitz-Araya X and Lazebnik Y . (2002). Science, 297, 1352–1354.

  • Leist M and Jäättelä M . (2001). Nat. Rev. Mol. Cell Biol., 2, 589–598.

  • Li LY, Luo X and Wang X . (2001). Nature, 412, 95–99.

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemeri ES and Wang X . (1997). Cell, 91, 479–489.

  • Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H and Levine B . (1999). Nature, 402, 672–676.

  • Liao DJ and Dickson RB . (2003). Lab. Invest., 83, 1437–1449.

  • Liossis SN, Ding XZ, Kiang JG and Tsokos GC . (1997). J. Immunol., 158, 5668–5675.

  • Liu N, Raja SM, Zazzeroni F, Metkar SS, Shah R, Zhang M, Wang Y, Bromme D, Russin WA, Lee JC, Peter ME, Froelich CJ, Franzoso G and Ashton-Rickardt PG . (2003). EMBO J., 22, 5313–5322.

  • Lockshin RA and Zakeri Z . (2002). Curr. Opin. Cell Biol., 14, 727–733.

  • Lotem J and Sachs L . (1996). Proc. Natl. Acad. Sci. USA, 93, 12507–12512.

  • Luo X, Budihardjo I, Zou H, Slaughter C and Wang X . (1998). Cell, 94, 481–490.

  • Luschen S, Ussat S, Scherer G, Kabelitz D and Adam-Klages S . (2000). J. Biol. Chem., 275, 24670–24678.

  • Madge LA, Li JH, Choi J and Pober JS . (2003). J. Biol. Chem., 278, 21295–21306.

  • Mateo V, Brown EJ, Biron G, Rubio M, Fischer A, Deist FL and Sarfati M . (2002). Blood, 100, 2882–2890.

  • Mateo V, Lagneaux L, Bron D, Biron G, Armant M, Delespesse G and Sarfati M . (1999). Nat. Med., 5, 1277–1284.

  • Mathiasen IS and Jäättelä M . (2002). Trends Mol. Med., 8, 212–220.

  • Mathiasen IS, Lademann U and Jäättelä M . (1999). Cancer Res., 59, 4848–4856.

  • Mathiasen IS, Sergeev IN, Bastholm L, Elling F, Norman AW and Jäättelä M . (2002). J. Biol. Chem., 277, 30738–30745.

  • Mattson MP, LaFerla FM, Chan SL, Leissring MA, Shepel PN and Geiger JD . (2000). Trends Neurosci., 23, 222–229.

  • Multhoff G, Botzler C, Jennen L, Schmidt J, Ellwart J and Issels R . (1997). J. Immunol., 158, 4341–4350.

  • Nakagawa T and Yuan J . (2000). J. Cell Biol., 150, 887–894.

  • Nylandsted J, Rohde M, Brand K, Bastholm L, Elling F and Jäättelä M . (2000). Proc. Natl. Acad. Sci. USA, 97, 7871–7876.

  • Nylandsted J, Wick W, Hirt UA, Brand K, Rohde M, Leist M, Weller M and Jäättelä M . (2002). Cancer Res., 62, 7139–7142.

  • Ogier-Denis E and Codogno P . (2003). Biochim. Biophys. Acta, 1603, 113–128.

  • Pattingre S, Bauvy C and Codogno P . (2003). J. Biol. Chem., 278, 16667–16674.

  • Pettersen RD, Bernard G, Olafsen MK, Pourtein M and Lie SO . (2001). J. Immunol., 166, 4931–4942.

  • Quignon F, De Bels F, Koken M, Feunteun J, Ameisen JC and de The H . (1998). Nat. Genet., 20, 259–265.

  • Raveh T, Droguett G, Horwitz MS, DePinho RA and Kimchi A . (2001). Nat. Cell Biol., 3, 1–7.

  • Raveh T and Kimchi A . (2001). Exp. Cell Res., 264, 185–192.

  • Reed JC . (2001). Trends Mol. Med., 7, 314–319.

  • Reggiori F and Klionsky DJ . (2002). Eukaryot. Cell, 1, 11–21.

  • Roberg K, Kagedal K and Ollinger K . (2002). Am. J. Pathol., 161, 89–96.

  • Roshy S, Sloane BF and Moin K . (2003). Cancer Metast. Rev., 22, 271–286.

  • Saeki K, Yuo A, Okuma E, Yazaki Y, Susin SA, Kroemer G and Takaku F . (2000). Cell Death Differ., 7, 1263–1269.

  • Sakahira H, Enari M and Nagata S . (1998). Nature, 391, 96–99.

  • Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH and Peter ME . (1998). EMBO J., 17, 1675–1687.

  • Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA and Fiers W . (1992). J. Biol. Chem., 267, 5317–5323.

  • Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T and Korsmeyer SJ . (2003). Science, 300, 135–139.

  • Scorrano L, Penzo D, Petronilli V, Pagano F and Bernardi P . (2001). J. Biol. Chem., 276, 12035–12040.

  • Semenza GL . (2003). Nat. Rev. Cancer, 3, 721–732.

  • Simpson L and Parsons R . (2001). Exp. Cell Res., 264, 29–41.

  • Sperandio S, de Belle I and Bredesen DE . (2000). Proc. Natl. Acad. Sci. USA, 97, 14376–14381.

  • Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP and Mak TW . (1998). Cell, 95, 29–39.

  • Strasser A, O'Connor L and Dixit VM . (2000). Annu. Rev. Biochem., 69, 217–245.

  • Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Constantini P, Loeffer M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM and Kroemer G . (1999). Nature, 397, 441–446.

  • Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K and Takahashi R . (2001). Mol. Cell, 8, 613–621.

  • Tal-Or P, Di-Segni A, Lupowitz Z and Pinkas-Kramarski R . (2003). Prostate, 55, 147–157.

  • Tamura T, Ishihara M, Lamphier MS, Tanaka N, Oishi I, Aizawa S, Matsuyama T, Mak TW, Taki S and Taniguchi T . (1995). Nature, 376, 596–599.

  • Tanaka N, Ishihara M, Kitagawa M, Harada H, Kimura T, Matsuyama T, Lamphier MS, Aizawa S, Mak TW and Taniguchi T . (1994). Cell, 77, 829–839.

  • Thome M and Tschopp J . (2001). Nat. Rev. Immunol., 1, 50–58.

  • Tolkovsky AM, Xue L, Fletcher GC and Borutaite V . (2002). Biochimie, 84, 233–240.

  • Torriglia A, Perani P, Brossas JY, Chaudun E, Treton J, Courtois Y and Counis MF . (1998). Mol. Cell. Biol., 18, 3612–3619.

  • Turk B, Stoka V, Rozman-Pungercar J, Cirman T, Droga-Mazovec G, Oreic K and Turk V . (2002). Biol. Chem., 383, 1035–1044.

  • Vancompernolle K, Van Herreweghe F, Pynaert G, Van de Craen M, De Vos K, Totty N, Sterling A, Fiers W, Vandenabeele P and Grooten J . (1998). FEBS Lett., 438, 150–158.

  • Vande Velde C, Cizeau J, Dubik D, Alimonti J, Brown T, Israels S, Hakem R and Greenberg AH . (2000). Mol. Cell. Biol., 20, 5454–5468.

  • van Eijk M and de Groot C . (1999). J. Immunol., 163, 2478–2482.

  • Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P and Wallach D . (1998). Immunity, 9, 267–276.

  • Vaux DL, Cory S and Adams JM . (1988). Nature, 335, 440–442.

  • Vercammen D, Beyaert R, Denecker G, Goossens V, Van Loo G, Declercq W, Grooten J, Fiers W and Vandenabeele P . (1998a). J. Exp. Med., 187, 1477–1485.

  • Vercammen D, Brouckaert G, Denecker G, Van de Craen M, Declercq W, Fiers W and Vandenabeele P . (1998b). J. Exp. Med., 188, 919–930.

  • Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, Adams JM and Strasser A . (2003). Science, 302, 1036–1038.

  • Von Ahsen O, Waterhouse NJ, Kuwana T, Newmeyer DD and Green DR . (2000). Cell Death Differ., 7, 1192–1199.

  • Vousden KH and Lu X . (2002). Nat. Rev. Cancer, 2, 594–604.

  • Wang C-Y, Mayo MW and Baldwin Jr AS . (1996). Science, 274, 784–787.

  • Wang KK . (2000). Trends Neurosci., 23, 20–26.

  • Wang X, Yang C, Chai J, Shi Y and Xue D . (2002). Science, 298, 1587–1592.

  • Wang ZG, Ruggero D, Ronchetti S, Zhong S, Gaboli M, Rivi R and Pandolfi PP . (1998). Nat. Genet., 20, 266–272.

  • Wilson CA and Browning JL . (2002). Cell Death Differ., 9, 1321–1333.

  • Wu GS, Saftig P, Peters C and El-Deiry WS . (1998). Oncogene, 16, 2177–2183.

  • Wu X and Levine AJ . (1994). Proc. Natl. Acad. Sci. USA, 91, 3602–3606.

  • Yanagisawa H, Miyashita T, Nakano Y and Yamamoto D . (2003). Cell Death Differ., 10, 798–807.

  • Yang S, Kuo C, Bisi JE and Kim MK . (2002). Nat. Cell Biol., 4, 865–870.

  • Yao XR and Scott DW . (1993). Proc. Natl. Acad. Sci. USA, 90, 7946–7950.

  • Yeh W-C, de la Pompa JL, McCurrach ME, Shu H-B, Elia AJ, Shahinian A, Ng M, Wakeman A, Khoo W, Mitchell K, El-Deiry WS, Lowe SW, Goeddel DV and Mak TW . (1998). Science, 279, 1954–1958.

  • Yonish-Rouach E, Resnitzky D, Lotem J, Sachs L, Kimchi A and Oren M . (1991). Nature, 352, 345–347.

  • Yuan XM, Li W, Dalen H, Lotem J, Kama R, Sachs L and Brunk UT . (2002). Proc. Natl. Acad. Sci. USA, 99, 6286–6291.

  • Zang Y, Beard RL, Chandraratna RA and Kang JX . (2001). Cell Death Differ., 8, 477–485.

  • Zanke BW, Lee C, Arab S and Tannock IF . (1998). Cancer Res., 58, 2801–2808.

  • Zhang J, Cado D, Chen A, Kabra NH and Winoto A . (1998). Nature, 392, 296–300.

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Jäättelä, M. Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene 23, 2746–2756 (2004). https://doi.org/10.1038/sj.onc.1207513

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