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Apoptotic Signaling Pathway and Resistance to Apoptosis in Breast Cancer Stem Cells

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Book cover Apoptosis in Carcinogenesis and Chemotherapy

Abstract

A major challenge in the treatment of human breast cancer is the development of resistant mechaims to apoptosis in cancer cells that leads to a low senstivity to therapeutic agents. Recent advances in investigation of the cellular origin of breast cancer showed that breast cancers can be derived from a few tumor initiating cells or cancer stem cells. Increasing evidence supports the notion that cancer stem cells are highly aggressive and resistant to conventional therapies, leading to the progression of breast cancer. Therefore, understanding the molecular mechanisms of differential regulation of the apoptitic signaling pathway in normal mammary epithelial cells, breast cancer stem cells, and breast cancer cells representing different stages of the disease should allow for the development of novel therapeutic approaches targeting dysfunctional apoptotic signaling pathways in breast cancer cells and/or cancer stem~cells.

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References

  • Abrams SI (2005) Positive and negative consequences of Fas/Fas ligand interactions in the antitumor response. Front Biosci 10:809–821

    PubMed  CAS  Google Scholar 

  • Adida C, Crotty PL, McGrath J, Berrebi D, Diebold J, Altieri DC (1998) Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 152:43–49

    PubMed  CAS  Google Scholar 

  • Aird KM, Ding X, Baras A, Wei J, Morse MA, Clay T, Lyerly HK, Devi GR (2008) Trastuzumab signaling in ErbB2-overexpressing inflammatory breast cancer correlates with X-linked inhibitor of apoptosis protein expression. Mol Cancer Ther 7:38–47

    PubMed  CAS  Google Scholar 

  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988

    PubMed  CAS  Google Scholar 

  • Alsabeh R, Wilson CS, Ahn CW, Vasef MA, Battifora H (1996) Expression of bcl-2 by breast cancer: a possible diagnostic application. Mod Pathol 9:439–444

    PubMed  CAS  Google Scholar 

  • Altieri DC (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 22:8581–8589

    PubMed  CAS  Google Scholar 

  • Amantana A, London CA, Iversen PL, Devi GR (2004) X-linked inhibitor of apoptosis protein inhibition induces apoptosis and enhances chemotherapy sensitivity in human prostate cancer cells. Mol Cancer Ther 3:699–707

    PubMed  CAS  Google Scholar 

  • Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921

    PubMed  CAS  Google Scholar 

  • Anderson TJ (1999) Pathological studies of apoptosis in the normal breast. Endocr Relat Cancer 6:9–12

    PubMed  CAS  Google Scholar 

  • Arora V, Cheung HH, Plenchette S, Micali OC, Liston P, Korneluk RG (2007) Degradation of survivin by the X-linked inhibitor of apoptosis (XIAP)-XAF1 complex. J Biol Chem 282:26202–26209

    PubMed  CAS  Google Scholar 

  • Barnhart BC, Legembre P, Pietras E, Bubici C, Franzoso G, Peter ME (2004) CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells. Embo J 23: 3175–3185

    PubMed  CAS  Google Scholar 

  • Basile JR, Zacny V, Munger K (2001) The cytokines tumor necrosis factor-alpha (TNF-alpha) and TNF-related apoptosis-inducing ligand differentially modulate proliferation and apoptotic pathways in human keratinocytes expressing the human papillomavirus-16 E7 oncoprotein. J Biol Chem 276: 22522–22528

    PubMed  CAS  Google Scholar 

  • Beltinger C, Bohler T, Schrappe M, Ludwig WD, Debatin KM (1998) [The role of CD95 (APO-1/Fas) mutations in lymphoproliferative and malignant lymphatic diseases]. Klin Padiatr 210:153–158

    PubMed  CAS  Google Scholar 

  • Boatright KM, Salvesen GS (2003) Mechanisms of caspase activation. Curr Opin Cell Biol 15:725–731

    PubMed  CAS  Google Scholar 

  • Bockbrader KM, Tan M, Sun Y (2005) A small molecule Smac-mimic compound induces apoptosis and sensitizes TRAIL- and etoposide-induced apoptosis in breast cancer cells. Oncogene 24:7381–7388

    PubMed  CAS  Google Scholar 

  • Bodis S, Siziopikou KP, Schnitt SJ, Harris JR, Fisher DE (1996) Extensive apoptosis in ductal carcinoma in situ of the breast. Cancer 77:1831–1835

    PubMed  CAS  Google Scholar 

  • Boldrini L, Faviana P, Gisfredi S, Di Quirico D, Lucchi M, Mussi A, Angeletti CA, Baldinotti F, Fogli A, Simi P, Basolo F, Pingitore F, Fontanini G (2002) Identification of Fas (APO-1/CD95) and p53 gene mutations in non-small cell lung cancer. Int J Oncol 20:155–159

    PubMed  CAS  Google Scholar 

  • Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    PubMed  CAS  Google Scholar 

  • Bullani RR, Wehrli P, Viard-Leveugle I, Rimoldi D, Cerottini JC, Saurat JH, Tschopp J, French LE (2002) Frequent downregulation of Fas (CD95) expression and function in melanoma. Melanoma Res 12:263–270

    PubMed  CAS  Google Scholar 

  • Cheng EH, Kirsch DG, Clem RJ, Ravi R, Kastan MB, Bedi A, Ueno K, Hardwick JM (1997) Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 278:1966–1968

    PubMed  CAS  Google Scholar 

  • Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ (2003) VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science 301:513–517

    PubMed  CAS  Google Scholar 

  • Cheng EH, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ (2001) BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell 8:705–711

    PubMed  CAS  Google Scholar 

  • Cheng JQ, Jiang X, Fraser M, Li M, Dan HC, Sun M, Tsang BK (2002) Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway. Drug Resist Updat 5:131–146

    PubMed  CAS  Google Scholar 

  • Chinnaiyan AM, Tepper CG, Seldin MF, O’Rourke K, Kischkel FC, Hellbardt S, Krammer PH, Peter ME, Dixit VM (1996) FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 271:4961–4965

    PubMed  CAS  Google Scholar 

  • Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010–1014

    PubMed  CAS  Google Scholar 

  • Clem RJ, Cheng EH, Karp CL, Kirsch DG, Ueno K, Takahashi A, Kastan MB, Griffin DE, Earnshaw WC, Veliuona MA, Hardwick JM (1998) Modulation of cell death by Bcl-XL through caspase interaction. Proc Natl Acad Sci USA 95:554–559

    PubMed  CAS  Google Scholar 

  • Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65:10946–10951

    PubMed  CAS  Google Scholar 

  • Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2:647–656

    PubMed  CAS  Google Scholar 

  • Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341:233–249

    PubMed  CAS  Google Scholar 

  • Cummings J, Ranson M, Lacasse E, Ganganagari JR, St-Jean M, Jayson G, Durkin J, Dive C (2006) Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP. Br J Cancer 95:42–48

    PubMed  CAS  Google Scholar 

  • Debnath J, Mills KR, Collins NL, Reginato MJ, Muthuswamy SK, Brugge JS (2002) The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini. Cell 111:29–40

    PubMed  CAS  Google Scholar 

  • Deveraux QL, Reed JC (1999) IAP family proteins – suppressors of apoptosis. Genes Dev 13: 239–252

    PubMed  CAS  Google Scholar 

  • Dohi T, Okada K, Xia F, Wilford CE, Samuel T, Welsh K, Marusawa H, Zou H, Armstrong R, Matsuzawa S, Salvesen GS, Reed JC, Altieri DC (2004) An IAP-IAP complex inhibits apoptosis. J Biol Chem 279:34087–34090

    PubMed  CAS  Google Scholar 

  • Elnemr A, Ohta T, Yachie A, Kayahara M, Kitagawa H, Fujimura T, Ninomiya I, Fushida S, Nishimura GI, Shimizu K, Miwa K (2001) Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway. Int J Oncol 18:311–316

    PubMed  CAS  Google Scholar 

  • Eramo A, Pallini R, Lotti F, Sette G, Patti M, Bartucci M, Ricci-Vitiani L, Signore M, Stassi G, Larocca LM, Crino L, Peschle C, De Maria R (2005) Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction. Cancer Res 65:11469–11477

    PubMed  CAS  Google Scholar 

  • Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G, Pilozzi E, Larocca LM, Peschle C, De Maria R (2006) Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ 13:1238–1241

    PubMed  CAS  Google Scholar 

  • Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG, Bundred NJ (2007) Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst 99:616–627

    PubMed  CAS  Google Scholar 

  • Fujikawa K, Shiraki K, Sugimoto K, Ito T, Yamanaka T, Takase K, Nakano T (2000) Reduced expression of ICE/caspase1 and CPP32/caspase3 in human hepatocellular carcinoma. Anticancer Res 20:1927–1932

    PubMed  CAS  Google Scholar 

  • Fukuda S, Mantel CR, Pelus LM (2004) Survivin regulates hematopoietic progenitor cell proliferation through p21WAF1/Cip1-dependent and -independent pathways. Blood 103:120–127

    PubMed  CAS  Google Scholar 

  • Fukuda S, Pelus LM (2006) Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther 5:1087–1098

    PubMed  CAS  Google Scholar 

  • Galligan L, Longley DB, McEwan M, Wilson TR, McLaughlin K, Johnston PG (2005) Chemotherapy and TRAIL-mediated colon cancer cell death: the roles of p53, TRAIL receptors, and c-FLIP. Mol Cancer Ther 4: 2026–2036

    PubMed  CAS  Google Scholar 

  • Gee JM, Robertson JF, Ellis IO, Willsher P, McClelland RA, Hoyle HB, Kyme SR, Finlay P, Blamey RW, Nicholson RI (1994) Immunocytochemical localization of BCL-2 protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy. Int J Cancer 59:619–628

    PubMed  CAS  Google Scholar 

  • Gilg AG, Tye SL, Tolliver LB, Wheeler WG, Visconti RP, Duncan JD, Kostova FV, Bolds LN, Toole BP, Maria BL (2008) Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors. Clin Cancer Res 14:1804–1813

    PubMed  CAS  Google Scholar 

  • Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    PubMed  CAS  Google Scholar 

  • Guo Y, Mantel C, Hromas RA, Broxmeyer HE (2008) Oct-4 is critical for survival/antiapoptosis of murine embryonic stem cells subjected to stress: effects associated with Stat3/survivin. Stem Cells 26:30–34

    PubMed  CAS  Google Scholar 

  • Hahm HA, Davidson NE (1998) Apoptosis in the mammary gland and breast cancer. Endocrine-Related Cancer 5:199–211

    CAS  Google Scholar 

  • Han ZB, Ren H, Zhao H, Chi Y, Chen K, Zhou B, Liu YJ, Zhang L, Xu B, Liu B, Yang R, Han ZC (2008) Hypoxia-inducible factor (HIF)-1{alpha} directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF). Carcinogenesis 29(10):1853–1861

    PubMed  CAS  Google Scholar 

  • Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776

    PubMed  CAS  Google Scholar 

  • Hopkins-Donaldson S, Ziegler A, Kurtz S, Bigosch C, Kandioler D, Ludwig C, Zangemeister-Wittke U, Stahel R (2003) Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ 10: 356–364

    PubMed  CAS  Google Scholar 

  • Hu Y, Cherton-Horvat G, Dragowska V, Baird S, Korneluk RG, Durkin JP, Mayer LD, LaCasse EC (2003) Antisense oligonucleotides targeting XIAP induce apoptosis and enhance chemotherapeutic activity against human lung cancer cells in vitro and in vivo. Clin Cancer Res 9:2826–2836

    PubMed  CAS  Google Scholar 

  • Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H (2001) Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain. Cell 104:781–790

    PubMed  CAS  Google Scholar 

  • Hughes PD, Belz GT, Fortner KA, Budd RC, Strasser A, Bouillet P (2008) Apoptosis regulators Fas and Bim cooperate in shutdown of chronic immune responses and prevention of autoimmunity. Immunity 28:197–205

    PubMed  CAS  Google Scholar 

  • Hutcheson J, Scatizzi JC, Siddiqui AM, Haines GK, 3rd, Wu T, Li QZ, Davis LS, Mohan C, Perlman H (2008) Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity. Immunity 28:206–217

    PubMed  CAS  Google Scholar 

  • Ibrahim SM, Ringel J, Schmidt C, Ringel B, Muller P, Koczan D, Thiesen HJ, Lohr M (2001) Pancreatic adenocarcinoma cell lines show variable susceptibility to TRAIL-mediated cell death. Pancreas 23:72–79

    PubMed  CAS  Google Scholar 

  • Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2:277–288

    PubMed  CAS  Google Scholar 

  • Iolascon A, Borriello A, Giordani L, Cucciolla V, Moretti A, Monno F, Criniti V, Marzullo A, Criscuolo M, Ragione FD (2003) Caspase 3 and 8 deficiency in human neuroblastoma. Cancer Genet Cytogenet 146:41–47

    PubMed  CAS  Google Scholar 

  • Jin Z, McDonald ER 3rd, Dicker DT, El-Deiry WS (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279:35829–35839

    PubMed  CAS  Google Scholar 

  • Joensuu H, Pylkkanen L, Toikkanen S (1994) Bcl-2 protein expression and long-term survival in breast cancer. Am J Pathol 145:1191–1198

    Google Scholar 

  • Kang MK, Kang SK (2007) Tumorigenesis of chemotherapeutic drug-resistant cancer stem-like cells in brain glioma. Stem Cells Dev 16:837–847

    PubMed  CAS  Google Scholar 

  • Karna P, Cao Z, Harris W, Oprea G, O’Regan, Waller RK, Wood WC, Yang L (2008) EGFR signal activated HIF-1 alpha/survivin pathway confers apoptosis resistance in CD44+ breast cancer stem cells. In: Proceedings of the 99th Annual Meeting of the American Association for Cancer Research; 2008 Apr 12–16, AACR, Philadelphia (PA), San Diego, CA, USA

    Google Scholar 

  • Kelekar A, Thompson CB (1998) Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8:324–330

    PubMed  CAS  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    PubMed  CAS  Google Scholar 

  • Keshet GI, Goldstein I, Yitzhaki O, Cesarkas K, Shenhav L, Yakirevitch A, Treves AJ, Schachter J, Amariglio N, Rechavi G (2008) MDR1 expression identifies human melanoma stem cells. Biochem Biophys Res Commun 368(4):930–936

    PubMed  CAS  Google Scholar 

  • Kestendjieva S, Kyurkchiev D, Tsvetkova G, Mehandjiev T, Dimitrov A, Nikolov A, Kyurkchiev S (2008) Characterization of mesenchymal stem cells isolated from the human umbilical cord. Cell Biol Int 32:724–732

    PubMed  CAS  Google Scholar 

  • Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T (2005) Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121:823–835

    PubMed  CAS  Google Scholar 

  • Kim K, Fisher MJ, Xu SQ, el-Deiry WS (2000) Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res 6:335–346

    PubMed  CAS  Google Scholar 

  • Kolenko V, Uzzo RG, Bukowski R, Bander NH, Novick AC, Hsi ED, Finke JH (1999) Dead or dying: necrosis versus apoptosis in caspase-deficient human renal cell carcinoma. Cancer Res 59:2838–2842

    PubMed  CAS  Google Scholar 

  • Krajewski S, Blomqvist C, Franssila K, Krajewska M, Wasenius VM, Niskanen E, Nordling S, Reed JC (1995) Reduced expression of proapoptotic gene BAX is associated with poor response rates to combination chemotherapy and shorter survival in women with metastatic breast adenocarcinoma. Cancer Res 55:4471–4478

    PubMed  CAS  Google Scholar 

  • Krajewski S, Krajewska M, Turner BC, Pratt C, Howard B, Zapata JM, Frenkel V, Robertson S, Ionov Y, Yamamoto H, Perucho M, Takayama S, Reed JC (1999) Prognostic significance of apoptosis regulators in breast cancer. Endocr Relat Cancer 6:29–40

    PubMed  CAS  Google Scholar 

  • Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795

    PubMed  CAS  Google Scholar 

  • Landowski TH, Moscinski L, Burke R, Buyuksal I, Painter JS, Goldstein S, Dalton WS (2001) CD95 antigen mutations in hematopoietic malignancies. Leuk Lymphoma 42: 835–846

    PubMed  CAS  Google Scholar 

  • Lee SH, Shin MS, Lee JY, Park WS, Kim SY, Jang JJ, Dong SM, Na EY, Kim CS, Kim SH, Yoo NJ (1999) In vivo expression of soluble Fas and FAP-1: possible mechanisms of Fas resistance in human hepatoblastomas. J Pathol 188:207–212

    PubMed  CAS  Google Scholar 

  • Leung CG, Xu Y, Mularski B, Liu H, Gurbuxani S, Orispino JD (2007) Requirements for survivin in terminal differentiations of erythroid cells and maintenance of Hematopoietic stem and progenitor cells. J Exp Med 204:1603–1611

    PubMed  CAS  Google Scholar 

  • Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (2007) Identification of pancreatic cancer stem cells. Cancer Res 67:1030–1037

    PubMed  CAS  Google Scholar 

  • Li F (2003) Survivin study: what is the next wave? J Cell Physiol 197:8–29

    PubMed  CAS  Google Scholar 

  • Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG (2004) A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death. Science 305: 1471–1474

    PubMed  CAS  Google Scholar 

  • Li QX, Zhao J, Liu JY, Jia LT, Huang HY, Xu YM, Zhang Y, Zhang R, Wang CJ, Yao LB, Chen SY, Yang AG (2006) Survivin stable knockdown by siRNA inhibits tumor cell growth and angiogenesis in breast and cervical cancers. Cancer Biol Ther 5:860–866

    PubMed  CAS  Google Scholar 

  • Li Y, Kong L, Yang Y, Li K (2007) Mutant TNFalpha negatively regulates human breast cancer stem cells from MCF7 in vitro. Cancer Biol Ther 6:1480–1489

    PubMed  CAS  Google Scholar 

  • Liang Y, Yan C, Schor NF (2001) Apoptosis in the absence of caspase 3. Oncogene 20: 6570–6578

    PubMed  CAS  Google Scholar 

  • Liston P, Fong WG, Kelly NL, Toji S, Miyazaki T, Conte D, Tamai K, Craig CG, McBurney MW, Korneluk RG (2001) Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol 3:128–133

    PubMed  CAS  Google Scholar 

  • Liu JH, Wei S, Lamy T, Li Y, Epling-Burnette PK, Djeu JY, Loughran TP Jr (2002) Blockade of Fas-dependent apoptosis by soluble Fas in LGL leukemia. Blood 100:1449–1453

    PubMed  CAS  Google Scholar 

  • Lou H, Dean M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26:1357–1360

    PubMed  CAS  Google Scholar 

  • Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21:485–495

    PubMed  CAS  Google Scholar 

  • Marconi A, Dallaglio K, Lotti R, Vaschieri C, Truzzi F, Fantini F, Pincelli C (2007) Survivin identifies keratinocyte stem cells and is downregulated by anti-beta1 integrin during anoikis. Stem Cells 25:149–155

    PubMed  CAS  Google Scholar 

  • Megha T, Ferrari F, Benvenuto A, Bellan C, Lalinga AV, Lazzi S, Bartolommei S, Cevenini G, Leoncini L, Tosi P (2002) p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin. J Clin Pathol 55:461–466

    PubMed  CAS  Google Scholar 

  • Meijnen P, Peterse JL, Antonini N, Rutgers EJ, van de Vijver MJ (2008) Immunohistochemical categorisation of ductal carcinoma in situ of the breast. Br J Cancer 98:137–142

    PubMed  CAS  Google Scholar 

  • Mesri M, Wall NR, Li J, Kim RW, Altieri DC (2001) Cancer gene therapy using a survivin mutant adenovirus. J Clin Invest 108:981–990

    PubMed  CAS  Google Scholar 

  • Miyake H, Hanada N, Nakamura H, Kagawa S, Fujiwara T, Hara I, Eto H, Gohji K, Arakawa S, Kamidono S, Saya H (1998) Overexpression of Bcl-2 in bladder cancer cells inhibits apoptosis induced by cisplatin and adenoviral-mediated p53 gene transfer. Oncogene 16:933–943

    PubMed  CAS  Google Scholar 

  • Miyake H, Hara I, Yamanaka K, Gohji K, Arakawa S, Kamidono S (1999) Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer cells. Br J Cancer 79:1651–1656

    PubMed  CAS  Google Scholar 

  • Miyashita T, Reed JC (1995) Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80:293–299

    PubMed  CAS  Google Scholar 

  • Morizane Y, Honda R, Fukami K, Yasuda H (2005) X-linked inhibitor of apoptosis functions as ubiquitin ligase toward mature caspase-9 and cytosolic Smac/DIABLO. J Biochem 137: 125–132

    PubMed  CAS  Google Scholar 

  • Motadi LR, Misso NL, Dlamini Z, Bhoola KD (2007) Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets. Int Immunopharmacol 7:1934–1947

    PubMed  CAS  Google Scholar 

  • Mullauer L, Mosberger I, Grusch M, Rudas M, Chott A (2000) Fas ligand is expressed in normal breast epithelial cells and is frequently up-regulated in breast cancer. J Pathol 190:20–30

    PubMed  CAS  Google Scholar 

  • Muschen M, Re D, Betz B, Moers C, Wolf J, Niederacher D, Diehl V, Beckmann MW (2001) Resistance to CD95-mediated apoptosis in breast cancer is not due to somatic mutation of the CD95 gene. Int J Cancer 92:309–310

    PubMed  CAS  Google Scholar 

  • Nakahara T, Takeuchi M, Kinoyama I, Minematsu T, Shirasuna K, Matsuhisa A, Kita A, Tominaga F, Yamanaka K, Kudoh M, Sasamata M (2007) YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res 67:8014–8021

    PubMed  CAS  Google Scholar 

  • Notarbartolo M, Cervello M, Poma P, Dusonchet L, Meli M, D’Alessandro N (2004) Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep 11:133–136

    PubMed  CAS  Google Scholar 

  • O’Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445:106–110

    PubMed  CAS  Google Scholar 

  • Odoux C, Albers A, Amoscato AA, Lotze MT, Wong MK (2002) TRAIL, FasL and a blocking anti-DR5 antibody augment paclitaxel-induced apoptosis in human non-small-cell lung cancer. Int J Cancer 97:458–465

    PubMed  CAS  Google Scholar 

  • Okada H, Mak TW (2004) Pathways of apoptotic and non-apoptotic death in tumour cells. Nat Rev Cancer 4:592–603

    PubMed  CAS  Google Scholar 

  • Oltvai ZN, Korsmeyer SJ (1994) Checkpoints of dueling dimers foil death wishes. Cell 79:189–192

    PubMed  CAS  Google Scholar 

  • Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902

    PubMed  CAS  Google Scholar 

  • Peng XH, Karna P, Cao Z, Jiang BH, Zhou M, Yang L (2006) Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J Biol Chem 281:25903–25914

    PubMed  CAS  Google Scholar 

  • Peter ME, Krammer PH (2003) The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 10:26–35

    PubMed  CAS  Google Scholar 

  • Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA 104:973–978

    PubMed  CAS  Google Scholar 

  • Reed JC (1998) Bcl-2 family proteins. Oncogene 17:3225–3236

    PubMed  Google Scholar 

  • Reed JC (2000) Mechanisms of apoptosis. Am J Pathol 157:1415–1430

    PubMed  CAS  Google Scholar 

  • Reed JC, Kroemer G (2000) Mechanisms of mitochondrial membrane permeabilization. Cell Death Differ 7:1145

    PubMed  CAS  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111

    PubMed  CAS  Google Scholar 

  • Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. Embo J 16:6914–6925

    PubMed  CAS  Google Scholar 

  • Sayers TJ, Brooks AD, Koh CY, Ma W, Seki N, Raziuddin A, Blazar BR, Zhang X, Elliott PJ, Murphy WJ (2003) The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP. Blood 102:303–310

    PubMed  CAS  Google Scholar 

  • Schorr K, Li M, Krajewski S, Reed JC, Furth PA (1999) Bcl-2 gene family and related proteins in mammary gland involution and breast cancer. J Mammary Gland Biol Neoplasia 4:153–164

    PubMed  CAS  Google Scholar 

  • Schulenburg A, Cech P, Herbacek I, Marian B, Wrba F, Valent P, Ulrich-Pur H (2007) CD44-positive colorectal adenoma cells express the potential stem cell markers musashi antigen (msi1) and ephrin B2 receptor (EphB2). J Pathol 213:152–160

    PubMed  CAS  Google Scholar 

  • Shankar S, Srivastava RK (2004) Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist Updat 7:139–156

    PubMed  CAS  Google Scholar 

  • Sheikh MS, Huang Y (2003) Death receptor activation complexes: it takes two to activate TNF receptor 1. Cell Cycle 2:550–552

    PubMed  CAS  Google Scholar 

  • Sherr CJ, McCormick F (2002) The RB and p53 pathways in cancer. Cancer Cell 2:103–112

    PubMed  CAS  Google Scholar 

  • Shin H, Okada K, Wilkinson JC, Solomon KM, Duckett CS, Reed JC, Salvesen GS (2003) Identification of ubiquitination sites on the X-linked inhibitor of apoptosis protein. Biochem J 373:965–971

    PubMed  CAS  Google Scholar 

  • Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI, Chung CW, Jung YK, Oh BH (2001) An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry 40:1117–1123

    PubMed  CAS  Google Scholar 

  • Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell 11: 259–273

    PubMed  CAS  Google Scholar 

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    PubMed  CAS  Google Scholar 

  • Singh TR, Shankar S, Chen X, Asim M, Srivastava RK (2003) Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Res 63:5390–5400

    PubMed  CAS  Google Scholar 

  • Soeda A, Inagaki A, Oka N, Ikegame Y, Aoki H, Yoshimura S, Nakashima S, Kunisada T, Iwama T (2008) Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells. J Biol Chem 283:10958–10966

    PubMed  CAS  Google Scholar 

  • Stroh C, Schulze-Osthoff K (1998) Death by a thousand cuts: an ever increasing list of caspase substrates. Cell Death Differ 5:997–1000

    PubMed  CAS  Google Scholar 

  • Sun H, Nikolovska-Coleska Z, Lu J, Meagher JL, Yang CY, Qiu S, Tomita Y, Ueda Y, Jiang S, Krajewski K, Roller PP, Stuckey JA, Wang S (2007) Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP. J Am Chem Soc 129: 15279–15294

    PubMed  CAS  Google Scholar 

  • Sun SY, Yue P, Zhou JY, Wang Y, Choi Kim HR, Lotan R, Wu GS (2001) Overexpression of BCL2 blocks TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. Biochem Biophys Res Commun 280:788–797

    PubMed  CAS  Google Scholar 

  • Suzuki Y, Nakabayashi Y, Takahashi R (2001) Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc Natl Acad Sci USA 98:8662–8667

    PubMed  CAS  Google Scholar 

  • Tamm I, Trepel M, Cardo-Vila M, Sun Y, Welsh K, Cabezas E, Swatterthwait A, Arap W, Reed JC, Pasqualini R (2003) Peptides targeting caspase inhibitors. J Biol Chem 278:14401–14405

    PubMed  CAS  Google Scholar 

  • Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC (1998) IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 58:5315–5320

    PubMed  CAS  Google Scholar 

  • Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N (2000) Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 6: 127–134

    PubMed  CAS  Google Scholar 

  • Teitz T, Wei T, Liu D, Valentine V, Valentine M, Grenet J, Lahti JM, Kidd VJ (2002) Caspase-9 and Apaf-1 are expressed and functionally active in human neuroblastoma tumor cell lines with 1p36 LOH and amplified MYCN. Oncogene 21:1848–1858

    PubMed  CAS  Google Scholar 

  • Thorburn A (2004) Death receptor-induced cell killing. Cell Signal 16:139–144

    PubMed  CAS  Google Scholar 

  • Tobiume K (2005) Involvement of Bcl-2 family proteins in p53-induced apoptosis. J Nippon Med Sch 72:192–193

    PubMed  Google Scholar 

  • Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389–402

    PubMed  CAS  Google Scholar 

  • Toole BP, Slomiany MG (2008) Hyaluronan, CD44 and Emmprin: Partners in cancer cell chemoresistance. Drug Resist Updat 11(3):110–121

    PubMed  CAS  Google Scholar 

  • Van Laethem A, Van Kelst S, Lippens S, Declercq W, Vandenabeele P, Janssens S, Vandenheede JR, Garmyn M, Agostinis P (2004) Activation of p38 MAPK is required for Bax translocation to mitochondria, cytochrome c release and apoptosis induced by UVB irradiation in human keratinocytes. Faseb J 18:1946–1948

    PubMed  Google Scholar 

  • van Noesel MM, van Bezouw S, Voute PA, Herman JG, Pieters R, Versteeg R (2003) Clustering of hypermethylated genes in neuroblastoma. Genes Chromosomes Cancer 38:226–233

    PubMed  Google Scholar 

  • Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJ, Flygare JA, Fairbrother WJ, Deshayes K, Dixit VM, Vucic D (2007) IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 131:669–681

    PubMed  CAS  Google Scholar 

  • Vaux DL, Silke J (2005) IAPs, RINGs and ubiquitylation. Nat Rev Mol Cell Biol 6:287–297

    PubMed  CAS  Google Scholar 

  • Viard-Leveugle I, Veyrenc S, French LE, Brambilla C, Brambilla E (2003) Frequent loss of Fas expression and function in human lung tumours with overexpression of FasL in small cell lung carcinoma. J Pathol 201:268–277

    PubMed  CAS  Google Scholar 

  • Villar E, Redondo M, Rodrigo I, Garcia J, Avila E, Matilla A (2001) bcl-2 Expression and apoptosis in primary and metastatic breast carcinomas. Tumour Biol 22:137–145

    PubMed  CAS  Google Scholar 

  • Vucic D, Fairbrother WJ (2007) The inhibitor of apoptosis proteins as therapeutic targets in cancer. Clin Cancer Res 13:5995–6000

    PubMed  CAS  Google Scholar 

  • Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5: 157–163

    PubMed  CAS  Google Scholar 

  • Wang Q, Greene MI (2005) EGFR enhances Survivin expression through the phosphoinositide 3 (PI-3) kinase signaling pathway. Exp Mol Pathol 79:100–107

    PubMed  CAS  Google Scholar 

  • Weant AE, Michalek RD, Khan IU, Holbrook BC, Willingham MC, Grayson JM (2008) Apoptosis regulators Bim and Fas function concurrently to control autoimmunity and CD8+ T cell contraction. Immunity 28:218–230

    PubMed  CAS  Google Scholar 

  • Wei C, Guo-min W, Yu-jun L (2006) Apoptosis resistance can be used in screening the markers of cancer stem cells. Med Hypotheses 67:1381–1383

    PubMed  Google Scholar 

  • Willis SN, Chen L, Dewson G, Wei A, Naik E, Fletcher JI, Adams JM, Huang DC (2005) Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 19:1294–1305

    PubMed  CAS  Google Scholar 

  • Woodward WA, Chen MS, Behbod F, Alfaro MP, Buchholz TA, Rosen JM (2007) WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells. Proc Natl Acad Sci USA 104:618–623

    PubMed  CAS  Google Scholar 

  • Xu JX, Morii E, Liu Y, Nakamichi N, Ikeda J, Kimura H, Aozasa K (2007) High tolerance to apoptotic stimuli induced by serum depletion and ceramide in side-population cells: high expression of CD55 as a novel character for side-population. Exp Cell Res 313:1877–1885

    PubMed  CAS  Google Scholar 

  • Yang E, Korsmeyer SJ (1996) Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 88:386–401

    PubMed  CAS  Google Scholar 

  • Yang L, Cao Z, Yan H, Wood WC (2003a) Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy. Cancer Res 63:6815–6824

    Google Scholar 

  • Yang L, Mashima T, Sato S, Mochizuki M, Sakamoto H, Yamori T, Oh-Hara T, Tsuruo T (2003b) Predominant suppression of apoptosome by inhibitor of apoptosis protein in non-small cell lung cancer H460 cells: therapeutic effect of a novel polyarginine-conjugated Smac peptide. Cancer Res 63:831–837

    Google Scholar 

  • Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, Chu PW, Lam CT, Poon RT, Fan ST (2008) Significance of CD90+ cancer stem cells in human liver cancer. Cancer Cell 13: 153–166

    PubMed  CAS  Google Scholar 

  • Zhang T, Otevrel T, Gao Z, Gao Z, Ehrlich SM, Fields JZ, Boman BM (2001) Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res 61:8664–8667

    PubMed  CAS  Google Scholar 

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  1. Department of Surgery and Radiology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA

    Prasanthi Karna

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  1. Prasanthi Karna
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  2. Lily Yang
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  1. Department of Surgery Shatin, Chinese University of Hong Kong Prince of Wales Hospital, Shatin, New Territories, Hong Kong/PR China

    George G. Chen Dr  & Paul B.S. Lai Dr  & 

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Karna, P., Yang, L. (2009). Apoptotic Signaling Pathway and Resistance to Apoptosis in Breast Cancer Stem Cells. In: Chen, G.G., Lai, P.B. (eds) Apoptosis in Carcinogenesis and Chemotherapy. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9597-9_1

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