Molecules and Cells

  • 제43권3호
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  • Pages.236-250
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  • 2020
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Inhibitory Role of TRIP-Br1/XIAP in Necroptosis under Nutrient/Serum Starvation

  • Sandag, Zolzaya (Department of Biological Science, Sookmyung Women's University) ;
  • Jung, Samil (Department of Biological Science, Sookmyung Women's University) ;
  • Quynh, Nguyen Thi Ngoc (Department of Biological Science, Sookmyung Women's University) ;
  • Myagmarjav, Davaajargal (Department of Biological Science, Sookmyung Women's University) ;
  • Anh, Nguyen Hai (Department of Biological Science, Sookmyung Women's University) ;
  • Le, Dan-Diem Thi (Department of Biological Science, Sookmyung Women's University) ;
  • Lee, Beom Suk (Department of Biological Science, Sookmyung Women's University) ;
  • Mongre, Raj Kumar (Department of Biological Science, Sookmyung Women's University) ;
  • Jo, Taeyeon (Department of Biological Science, Sookmyung Women's University) ;
  • Lee, MyeongSok (Department of Biological Science, Sookmyung Women's University)
  • 투고 : 2019.08.27
  • 심사 : 2020.01.02
  • 발행 : 2020.03.31
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초록

Currently, many available anti-cancer therapies are targeting apoptosis. However, many cancer cells have acquired resistance to apoptosis. To overcome this problem, simultaneous induction of other types of programmed cell death in addition to apoptosis of cancer cells might be an attractive strategy. For this purpose, we initially investigated the inhibitory role of TRIP-Br1/XIAP in necroptosis, a regulated form of necrosis, under nutrient/serum starvation. Our data showed that necroptosis was significantly induced in all tested 9 different types of cancer cell lines in response to prolonged serum starvation. Among them, necroptosis was induced at a relatively lower level in MCF-7 breast cancer line that was highly resistant to apoptosis than that in other cancer cell lines. Interestingly, TRIP-Br1 oncogenic protein level was found to be very high in this cell line. Up-regulated TRIP-Br1 suppressed necroptosis by repressing reactive oxygen species generation. Such suppression of necroptosis was greatly enhanced by XIAP, a potent inhibitor of apoptosis. Our data also showed that TRIP-Br1 increased XIAP phosphorylation at serine87, an active form of XIAP. Our mitochondrial fractionation data revealed that TRIP-Br1 protein level was greatly increased in the mitochondria upon serum starvation. It suppressed the export of CypD, a vital regulator in mitochondria-mediated necroptosis, from mitochondria to cytosol. TRIP-Br1 also suppressed shikonin-mediated necroptosis, but not TNF-α-mediated necroptosis, implying possible presence of another signaling pathway in necroptosis. Taken together, our results suggest that TRIP-Br1/XIAP can function as onco-proteins by suppressing necroptosis of cancer cells under nutrient/serum starvation.

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참고문헌

  1. Aharoni-Simon, M., Shumiatcher, R., Yeung, A., Shih, A.Z.L., Dolinsky, V.W., Doucette, C.A., and Luciani, D.S. (2016). Bcl-2 regulates reactive oxygen species signaling and a redox-sensitive mitochondrial proton leak in mouse pancreatic ${\beta}$-cells. Endocrinology 157, 2270-2281. https://doi.org/10.1210/en.2015-1964
  2. Belizario, J., Vieira-Cordeiro, L., and Enns, S. (2015). Necroptotic cell death signaling and execution pathway: lessons from knockout mice. Mediators Inflamm. 2015, 128076. https://doi.org/10.1155/2015/128076
  3. Berezovskaya, O., Schimmer, A.D., Glinskii, A.B., Pinilla, C., Hoffman, R.M., Reed, J.C., and Glinsky, G.V. (2005). Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells increased expression of apoptosis inhibitor protein XIAPcontributes to anoikis resistance of circul. Cancer Res. 65, 2378-2386. https://doi.org/10.1158/0008-5472.CAN-04-2649
  4. Berghe, T., Vanden, Linkermann, A., Jouan-Lanhouet, S., Walczak, H., and Vandenabeele, P. (2014). Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 15, 135-147. https://doi.org/10.1038/nrm3737
  5. Bernardi, P., Krauskopf, A., Basso, E., Petronilli, V., Blalchy-Dyson, E., Di Lisa, F., and Forte, M.A. (2006). The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J. 273, 2077-2099. https://doi.org/10.1111/j.1742-4658.2006.05213.x
  6. Cai, Z., Jitkaew, S., Zhao, J., Chiang, H.C., Choksi, S., Liu, J., Ward, Y., Wu, L.G., and Liu, Z.G. (2014). Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat. Cell Biol. 16, 55-65. https://doi.org/10.1038/ncb2883
  7. Chai, J., Shiozaki, E., Srinivasula, S.M., Wu, Q., Datta, P., Alnemri, E.S., and Shi, Y. (2001). Structural basis of caspase-7 inhibition by XIAP. Cell 104, 769-780. https://doi.org/10.1016/S0092-8674(01)00272-0
  8. Chan, F.K.-M., Luz, N.F., and Moriwaki, K. (2015). Programmed necrosis in the cross talk of cell death and inflammation. Annu. Rev. Immunol. 33, 79-106. https://doi.org/10.1146/annurev-immunol-032414-112248
  9. Christofferson, D.E. and Yuan, J. (2010). Cyclophilin a release as a biomarker of necrotic cell death. Cell Death Differ. 17, 1942-1943. https://doi.org/10.1038/cdd.2010.123
  10. Dan, H.C., Sun, M., Kaneko, S., Feldman, R.I., Nicosia, S.V., Wang, H.G., Tsang, B.K., and Cheng, J.Q. (2004). Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J. Biol. Chem. 279, 5405-5412. https://doi.org/10.1074/jbc.M312044200
  11. Dasgupta, A., Nomura, M., Shuck, R., and Yustein, J. (2017). Cancer's Achilles' heel: apoptosis and necroptosis to the rescue. Int. J. Mol. Sci. 18, 1-20. https://doi.org/10.3390/ijms18010001
  12. Dashzeveg, N. and Yoshida, K. (2015). Cell death decision by p53 via control of the mitochondrial membrane. Cancer Lett. 367, 108-112. https://doi.org/10.1016/j.canlet.2015.07.019
  13. De Almagro, M.C. and Vucic, D. (2015). Necroptosis: pathway diversity and characteristics. Semin. Cell Dev. Biol. 39, 56-62. https://doi.org/10.1016/j.semcdb.2015.02.002
  14. Deveraux, Q.L., Leo, E., Stennicke, H.R., Welsh, K., Salvesen, G.S., Reed, J.C., Boldin, M., Goncharov, T., Goltsev, Y., Wallach, D., et al. (1999). Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J. 18, 5242-5251. https://doi.org/10.1093/emboj/18.19.5242
  15. Dondelinger, Y., Hulpiau, P., Saeys, Y., Bertrand, M.J.M., and Vandenabeele, P. (2016). An evolutionary perspective on the necroptotic pathway. Trends Cell Biol. 26, 721-732. https://doi.org/10.1016/j.tcb.2016.06.004
  16. Duckett, C.S., Li, F., Wang, Y., Tomaselli, K.J., Thompson, C.B., and Armstrong, R.C. (1998). Human Iap-like protein regulates programmed cell death downstream of Bcl-X(L) and cytochrome C. Mol. Cell. Biol. 18, 608-615. https://doi.org/10.1128/MCB.18.1.608
  17. Eigenbrod, T., Park, J.H., Harder, J., Iwakura, Y., and Nunez, G. (2008). Cutting edge: critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1 alpha released from dying cells. J. Immunol. 181, 8194-8198. https://doi.org/10.4049/jimmunol.181.12.8194
  18. Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D.M., Forman, D., and Bray, F. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359-E386. https://doi.org/10.1002/ijc.29210
  19. Fulda, S. (2013). The mechanism of necroptosis in normal and cancer cells. Cancer Biol. Ther. 14, 999-1004. https://doi.org/10.4161/cbt.26428
  20. Geou-Yarh Liou, P.S. (2010). Reactive oxygen species in cancer. Free Radic. Res. 44, 47-49. https://doi.org/10.3109/10715760903321804
  21. Gonzalez-Juarbe, N., Gilley, R.P., Hinojosa, C.A., Bradley, K.M., Kamei, A., Gao, G., Dube, P.H., Bergman, M.A., and Orihuela, C.J. (2015). Pore-forming toxins induce macrophage necroptosis during acute bacterial pneumonia. PLoS Pathog. 11, 1-23.
  22. Halestrap, A.P. (2009). Mitochondria and reperfusion injury of the heart-A holey death but not beyond salvation. J. Bioenerg. Biomembr. 41, 113-121. https://doi.org/10.1007/s10863-009-9206-x
  23. Han, W., Li, L., Qiu, S., Lu, Q., Pan, Q., Gu, Y., Luo, J., and Hu, X. (2007). Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol. Cancer Ther. 6, 1641-1649. https://doi.org/10.1158/1535-7163.MCT-06-0511
  24. Hanahan, D. and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674. https://doi.org/10.1016/j.cell.2011.02.013
  25. He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., and Wang, X. (2009). Receptor interacting protein Kinase-3 determines cellular necrotic response to TNF-${\alpha}$. Cell 137, 1100-1111. https://doi.org/10.1016/j.cell.2009.05.021
  26. Hong, S.W., Kim, C.J., Park, W.S., Shin, J.S., Lee, S.D., Ko, S.G., Jung, S.I., Park, I.C., An, S.K., Lee, W.K., et al. (2009). p34SEI-1 inhibits apoptosis through the stabilization of the X-linked inhibitor of apoptosis protein: p34SEI-1 as a novel target for anti-breast cancer strategies. Cancer Res. 69, 741-746. https://doi.org/10.1158/0008-5472.CAN-08-1189
  27. Hong, S.W., Shin, J.S., Lee, Y.M., Kim, D.G., Lee, S.Y., Yoon, D.H., Jung, S.Y., Hwang, J.J., Lee, S.J., Cho, D.H., et al. (2011). p34SEI-1 inhibits ROS-induced cell death through suppression of ASK1. Cancer Biol. Ther. 12, 421-426. https://doi.org/10.4161/cbt.12.5.15972
  28. Hsu, S.I.H., Yang, C.M., Sim, K.G., Hentschel, D.M., O'leary, E., and Bonventre, J.V. (2001). TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1. EMBO J. 20, 2273-2285. https://doi.org/10.1093/emboj/20.9.2273
  29. Izuishi, K., Kato, K., Ogura, T., Kinoshita, T., and Esumi, H. (2000). Remarkable tolerance of tumor cells to nutrient deprivation: possible new biochemical target for cancer therapy. Cancer Res. 60, 6201-6207.
  30. Jouan-Lanhouet, S., Riquet, F., Duprez, L., Vanden Berghe, T., Takahashi, N., and Vandenabeele, P. (2014). Necroptosis, in vivo detection in experimental disease models. Semin. Cell Dev. Biol. 35, 2-13. https://doi.org/10.1016/j.semcdb.2014.08.010
  31. Jung, S., Li, C., Duan, J., Lee, S., Kim, K., Park, Y., Yang, Y., Kim, K., Lim, J., Cheon, C., et al. (2015). TRIP-Br1 oncoprotein inhibits autophagy, apoptosis, and necroptosis under nutrient/serum-deprived condition. Oncotarget 6, 29060-29075. https://doi.org/10.18632/oncotarget.5072
  32. Jung, S., Li, C., Jeong, D., Lee, S., Ohk, J., Park, M., Han, S., Duan, J., Kim, C., Yang, Y., et al. (2013). Oncogenic function of p34SEI-1 via NEDD4-1-mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway. Int. J. Oncol. 43, 1587-1595. https://doi.org/10.3892/ijo.2013.2064
  33. Jung, S., Ohk, J., Jeong, D., Li, C., Lee, S., Duan, J., Kim, C., Lim, J.S., Yang, Y., Kim, K.I.L., et al. (2014). Distinct regulatory effect of the p34SEI- 1oncoprotein on cancer metastasis in HER2/neu-positive and -negative cells. Int. J. Oncol. 45, 189-196. https://doi.org/10.3892/ijo.2014.2403
  34. Kaczmarek, A., Vandenabeele, P., and Krysko, D.V. (2013). Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity 38, 209-223. https://doi.org/10.1016/j.immuni.2013.02.003
  35. Karch, J., Kanisicak, O., Brody, M.J., Sargent, M.A., Michael, D.M., and Molkentin, J.D. (2015). Necroptosis interfaces with MOMP and the MPTP in mediating cell death. PLoS One 10, 1-12.
  36. Karch, J., Kwong, J.Q., Burr, A.R., Sargent, M.A., Elrod, J.W., Peixoto, P.M., Martinez-Caballero, S., Osinska, H., Cheng, E.H.Y., Robbins, J., et al. (2013). Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice. Elife 2013, 1-21.
  37. Kato, K., Tanaka, T., Sadik, G., Baba, M., Maruyama, D., Yanagida, K., Kodama, T., Morihara, T., Tagami, S., OKOCHI, M., et al. (2011). Protein kinase C stabilizes X-linked inhibitor of apoptosis protein (XIAP) through phosphorylation at Ser87 to suppress apoptotic cell death. Psychogeriatrics 11, 90-97. https://doi.org/10.1111/j.1479-8301.2011.00355.x
  38. Lee, S., Kim, J., Jung, S., Li, C., Yang, Y., Kim, K. I., Lim, J.S., Kim, Y., Cheon, C. Il, and Lee, M.S. (2015). SIAH1-induced p34SEI-1polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity. Int. J. Oncol. 46, 1377-1384. https://doi.org/10.3892/ijo.2015.2840
  39. Lee, S.L.O., Hong, S.W., Shin, J.S., Kim, J.S., Ko, S.G., Hong, N.J., Kim, D.J., Lee, W.J., Jin, D.H., and Lee, M.S. (2009). p34SEI-1 inhibits doxorubicin-induced senescence through a pathway mediated by protein kinase C-delta and c-Jun-NH2-kinase 1 activation in human breast cancer MCF7 cells. Mol. Cancer Res. 7, 1845-1853. https://doi.org/10.1158/1541-7786.MCR-09-0086
  40. Li, C., Jung, S., Lee, S., Jeong, D., Yang, Y., Kim, K.I., Lim, J., Cheon, C., Kim, C., and Lee, M. (2015). Nutrient/serum starvation derived TRIP-Br3 downregulation accelerates apoptosis by destabilizing XIAP. Oncotarget 6, 7522-7535. https://doi.org/10.18632/oncotarget.3112
  41. Lin, Y., Choksi, S., Shen, H.M., Yang, Q.F., Hur, G.M., Kim, Y.S., Tran, J.H., Nedospasov, S.A., and Liu, Z.G. (2004).Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J. Biol. Chem. 279, 10822-10828. https://doi.org/10.1074/jbc.M313141200
  42. Lindqvist, L.M., Heinlein, M., Huang, D.C.S., and Vaux, D.L. (2014). Prosurvival Bcl-2 family members affect autophagy only indirectly, by inhibiting Bax and Bak. Proc. Natl. Acad. Sci. U. S. A. 111, 8512-8517. https://doi.org/10.1073/pnas.1406425111
  43. Marchi, S., Giorgi, C., Suski, J.M., Agnoletto, C., Bononi, A., Bonora, M., De Marchi, E., Missiroli, S., Patergnani, S., Poletti, F., et al. (2012). Mitochondria-ROS crosstalk in the control of cell death and aging. J. Signal Transduct. 2012, 1-17.
  44. Marshall, K.D. and Baines, C.P. (2014). Necroptosis: is there a role for mitochondria? Front. Physiol. 5, 1-5. https://doi.org/10.3389/fphys.2014.00001
  45. Mizutani, Y., Nakanishi, H., Li, Y.N., Matsubara, H., Yamamoto, K., Sato, N., Shiraishi, T., Nakamura, T., Mikami, K., Okihara, K., et al. (2007). Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis. Int. J. Oncol. 30, 919-925.
  46. Montero, J., Dutta, C., Van Bodegom, D., Weinstock, D., and Letai, A. (2013). P53 regulates a non-apoptotic death induced by ROS. Cell Death Differ. 20, 1465-1474. https://doi.org/10.1038/cdd.2013.52
  47. Moriwaki, K., Bertin, J., Gough, P.J., Orlowski, G.M., and Chan, F.K. (2015). Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death. Cell Death Dis. 6, e1636. https://doi.org/10.1038/cddis.2015.16
  48. Newton, K. and Manning, G. (2016). Necroptosis and inflammation. Annu. Rev. Biochem. 85, 743-763. https://doi.org/10.1146/annurev-biochem-060815-014830
  49. Nikoletopoulou, V., Markaki, M., Palikaras, K., and Tavernarakis, N. (2013). Crosstalk between apoptosis, necrosis and autophagy. Biochim. Biophys. Acta - Mol. Cell Res. 1833, 3448-3459. https://doi.org/10.1016/j.bbamcr.2013.06.001
  50. Pasparakis, M. and Vandenabeele, P. (2015). Necroptosis and its role in inflammation. Nature 517, 311-320. https://doi.org/10.1038/nature14191
  51. Redza-Dutordoir, M. and Averill-Bates, D.A. (2016). Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta - Mol. Cell Res. 1863, 2977-2992. https://doi.org/10.1016/j.bbamcr.2016.09.012
  52. Riedl, S.J., Renatus, M., Schwarzenbacher, R., Zhou, Q., Sun, C., Fesik, S.W., Liddington, R.C., and Salvesen, G.S. (2001). Structural basis for the inhibition of caspase-3 by XIAP. Cell 104, 791-800. https://doi.org/10.1016/S0092-8674(01)00274-4
  53. Rohde, K., Kleinesudeik, L., Roesler, S., Lowe, O., Heidler, J., Schroder, K., Wittig, I., Drose, S., and Fulda, S. (2017). A Bak-dependent mitochondrial amplification step contributes to Smac mimetic/glucocorticoid-induced necroptosis. Cell Death Differ. 24, 83-97. https://doi.org/10.1038/cdd.2016.102
  54. Shiozaki, E.N., Chai, J., Rigotti, D.J., Riedl, S.J., Li, P., Srinivasula, S.M., Alnemri, E.S., Fairman, R., and Shi, Y. (2003). Mechanism of XIAP-mediated inhibition of caspase-9. Mol. Cell 11, 519-527. https://doi.org/10.1016/S1097-2765(03)00054-6
  55. Su, Z., Yang, Z., Xie, L., DeWitt, J.P., and Chen, Y. (2016). Cancer therapy in the necroptosis era. Cell Death Differ. 23, 748-756. https://doi.org/10.1038/cdd.2016.8
  56. Su, Z., Yang, Z., Xu, Y., Chen, Y., and Yu, Q. (2015). Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol. Cancer 14, 48. https://doi.org/10.1186/s12943-015-0321-5
  57. Sugimoto, M., Nakamura, T., Ohtani, N., Hampson, L., Hampson, I.N., Shimamoto, A., Furuichi, Y., Okumura, K., Niwa, S., Taya, Y., et al. (1999). Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1). Genes Dev. 13, 3027-3033. https://doi.org/10.1101/gad.13.22.3027
  58. Tang, D.J., Hu, L., Xie, D., Wu, Q.L., Fang, Y., Zeng, Y., Sham, J.S.T., and Guan, X.Y. (2005). Oncogenic transformation by SEI-1 is associated with chromosomal instability. Cancer Res. 65, 6504-6508. https://doi.org/10.1158/0008-5472.CAN-05-0351
  59. Tang, T.C., Sham, J.S.T., Xie, D., Cancer, O., and Lines, C. (2002). Identification of a Candidate Oncogene SEI-1 within a minimal amplified region at 19q13.1 in ovarian cancer cell lines advances in brief identification of a candidate oncogene SEI-1 within a minimal amplified region. Cancer Res. 62, 7157-7161.
  60. Teng, X., Degterev, A., Jagtap, P., Xing, X., Choi, S., Denu, R., Yuan, J., and Cuny, G.D. (2005). Structure-activity relationship study of novel necroptosis inhibitors. Bioorg. Med. Chem. Lett. 15, 5039-5044. https://doi.org/10.1016/j.bmcl.2005.07.077
  61. Tsujimoto, Y. and Shimizu, S. (2007). Role of the mitochondrial membrane permeability transition in cell death. Apoptosis 12, 835-840. https://doi.org/10.1007/s10495-006-0525-7
  62. Van Themsche, C., Leblanc, V., Parent, S., and Asselin, E. (2009). X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization. J. Biol. Chem. 284, 20462-20466. https://doi.org/10.1074/jbc.C109.009522
  63. Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., and Kroemer, G. (2010). Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat. Rev. Mol. Cell Biol. 11, 700-714. https://doi.org/10.1038/nrm2970
  64. Vaseva, A.V., Marchenko, N.D., Ji, K., Tsirka, S.E., Holzmann, S., and Moll, U.M. (2012). P53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 149, 1536-1548. https://doi.org/10.1016/j.cell.2012.05.014
  65. Wang, H., Sun, L., Su, L., Rizo, J., Liu, L., Wang, L.F., Wang, F.S., and Wang, X. (2014). Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol. Cell 54, 133-146. https://doi.org/10.1016/j.molcel.2014.03.003
  66. Wang, Z., Jiang, H., Chen, S., Du, F., and Wang, X. (2012). The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell 148, 228-243. https://doi.org/10.1016/j.cell.2011.11.030
  67. Wang, Z., Kishimoto, H., Bhat-Nakshatri, P., Crean, C., and Nakshatri, H. (2005). $TNF{\alpha}$ resistance in MCF-7 breast cancer cells is associated with altered subcellular localization of p21CIP1and p27KIP1[4]. Cell Death Differ. 12, 98-100. https://doi.org/10.1038/sj.cdd.4401515
  68. Xu, Y.Z., Kanagaratham, C., Youssef, M., and Radzioch, D. (2016). New frontiers in cancer chemotherapy: targeting cell death pathways. In Cell Biology: New Insights, S. Najman, ed. (Rijeka, Croatia: InTech), pp. 93-140.

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