Cancer is cell fleeing from death by blocking the intrinsic and extrinsic programs of cell death. The six elements that shut down those programs are: muc-1, muc-4, muc-16, Bcl-2, MMPs and decoy R3. The nuclear factor-kappa B (NF-Kb) stimulates the expression of genes responsible for the production of those elements, which are used by cells to block those two programs. In other words, the nuclear factor kappa B (NF-KB) is responsible for blocking both programs. Therefore, the nuclear factor kappa B (NF-Kb) is the true cause of cancer.
References
[1]
Anand, P., Kunnumakkara, A.B., Kunnumakara, A.B., Sundaram, C., Harikumar, K.B., Tharakan, S.T., Lai, O.S., Sung, B. and Aggarwal, B.B. (2008) Cancer Is a Preventable Disease that Requires Major Lifestyle Changes. Pharmaceutical Research, 25, 2097-2116. https://doi.org/10.1007/s11095-008-9661-9
[2]
Biesalski, H.K., Bueno de Mesquita, B., Chesson, A., Chytil, F., Grimble, R., Hermus, R.J., Köhrle, J., Lotan, R., Norpoth, K., Pastorino, U. and Thurnham, D. (1998) European Consensus Statement on Lung Cancer: Risk Factors and Prevention. Lung Cancer Panel. CA: A Cancer Journal for Clinicians, 48, 167-176. https://doi.org/10.3322/canjclin.48.3.167
[3]
Kuper, H., Adami, H.O. and Boffetta, P. (2002) Tobacco Use, Cancer Causation and Public Health Impact. Journal of Internal Medicine, 251, 455-466. https://doi.org/10.1046/j.1365-2796.2002.00993.x
[4]
Kushi, L.H., Byers, T., Doyle, C., Bandera, E.V., McCullough, M., McTiernan, A., Gansler, T., Andrews, K.S. and Thun, M.J. (2006) American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: Reducing the Risk of Cancer with Healthy Food Choices and Physical Activity. CA: A Cancer Journal for Clinicians, 56, 254-281. https://doi.org/10.3322/canjclin.56.5.254
[5]
Pagano, J.S., Blaser, M., Buendia, M.A., Damania, B., Khalili, K., Raab-Traub, N. and Roizman, B. (2004) Infectious Agents and Cancer: Criteria for a Causal Relation. Seminars in Cancer Biology, 14, 453-471. https://doi.org/10.1016/j.semcancer.2004.06.009
[6]
Ljubojevic, S. and Skerlev, M. (2014) HPV-Associated Diseases. Clinics in Dermatology, 32, 227-234. https://doi.org/10.1016/j.clindermatol.2013.08.007
[7]
Samaras, V., Rafailidis, P.I., Mourtzoukou, E.G., Peppas, G. and Falagas, M.E. (2010) Chronic Bacterial and Parasitic Infections and Cancer: A Review (PDF). Journal of Infection in Developing Countries, 4, 267-281.
Henderson, B.E., Bernstein, L. and Ross, R.K. (2000) Chapter 13: Hormones and the Etiology of Cancer. In: Bast, R.C., Kufe, D.W., Pollock, R.E., et al., Eds., Holland-Frei Cancer Medicine, 5th ed., B.C. Decker, Hamilton.
[10]
Roukos, D.H. (2009) Genome-Wide Association Studies: How Predictable Is a Person’s Cancer Risk? Expert Review of Anticancer Therapy, 9, 389-392. https://doi.org/10.1586/era.09.12
[11]
El-Khodary, M.S.M. (2018) Quranic Verse No. 8 of Surat Al-Jumu’ah Describes Cancer as a Complete and Accurate Description and Leads Us to Determine the True Cause of Cancer. “Part-1”. CellBio, 7, 1-11.
[12]
Kucharczak, J., Simmons, M.J., Fan, Y. and Getinas, C. (2003) To Be, or Not to Be: NF-KB Is the Answer-Role of Rel /NF-Kb in the Regulation of Apoptosis. Oncogene, 22, 8961-8982.
[13]
Lin, A. and Karin, M. (2003) NF-Kappa B in Cancer: A Marked Target. Seminars in Cancer Biology, 13, 107-114. https://doi.org/10.1016/S1044-579X(02)00128-1
[14]
Wang, T., Zhang, X. and Li, J.J. (2002) The Role of NF-Kb in the Regulation of Cell Stress Responses. International Immunopharmacology, 2, 1509-1520. https://doi.org/10.1016/S1567-5769(02)00058-9
[15]
Schmid, B.H. and Johannes, A. (2013) The Complexity of NF-Kb Signaling in Inflammation and Cancer. Molecular Cancer, 12, 68.
[16]
Schreck, R., Rieber, P. and Baeuerle, P.A. (1991) Reactive Oxygen Intermediates as Apparently Widely Used Messengers in the Activation of the NF-Kappa B Transcription Factor and HIV-1. The EMBO Journal, 10, 2247-2258.
[17]
Baldwin, A.S. (1996) The NF-KB and IkB Protein: New Discoveries and Insights. Annual Review of Immunology, 14, 649-683. https://doi.org/10.1146/annurev.immunol.14.1.649
[18]
Ghost, S., May, M.J. and Kopp, E.B. (1998) NF-KB and Rel Proteins: Evolutionarily Conserved Mediators of Immune Responses. Annual Review of Immunology, 16, 225-260. https://doi.org/10.1146/annurev.immunol.16.1.225
[19]
Dobrzanski, P., Ryseck, R.P. and Bravo, R. (1993) Both N- and C-Terminal Domains of RelB Are Required for Full Transactivation: Role of the N-Terminal Leucine Zipper-Like Motif. Molecular and Cellular Biology, 13, 1572-1582. https://doi.org/10.1128/MCB.13.3.1572
[20]
Hayden, M.S. and Ghosh, S. (2004) Signaling to NF-kappaB. Genes & Development, 18, 2195-2224.
[21]
Baeuerle, P.A. and Henkel, T. (1994) Function and Activation of NF-kappaB in the Immune System. Annual Review of Immunology, 12, 141-179. https://doi.org/10.1146/annurev.iy.12.040194.001041
[22]
Zandi, E. and Karin, M. (1999) Bridging the Gap: Composition, Regulation and Physiological Function of the IkB Kinase Complex. Molecular and Cellular Biology, 19, 4547-4551. https://doi.org/10.1128/MCB.19.7.4547
[23]
Gloire, G. and Piette, J. (2009) Redox Regulation of Nuclear Post-Translation Modification during NF-kb Activation. Antioxidants & Redox Signaling, 11, 2209-2222. https://doi.org/10.1089/ars.2009.2463
[24]
Catz, S.D. and Johnson, J.L. (2001) Transcriptional Regulation of bcl-2 by Nuclear Factor Kappa B and Its Significance in Prostate Cancer. Oncogene, 20, 7342-7351. https://doi.org/10.1038/sj.onc.1204926
[25]
Wang, C.Y., Mayo, M.W., Korneluk, R.G., Goeddel, D.V. and Baldwin, A.S. (1998) NF-Kb Anti-Apoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation. Science, 281, 1680-1683. https://doi.org/10.1126/science.281.5383.1680
[26]
Wu, M.X., Ao, Z., Prasad, K.V., Wu, R. and Schlossman, S.F. (1998) An Apoptosis Inhibitor Involved in NF-Kb Mediated Cell Survival. Science, 281, 998-1001. https://doi.org/10.1126/science.281.5379.998
[27]
O’Brien, T.J., Beard, J.B., Underwood, L.J. and Shigemasa, K. (2002) The CA125 Gene: A Newly Discovered Extension of Glycosylated N-Terminal Domain Doubles the Size of This Extracellular Superstructure. Tumor Biology, 23, 154-169. https://doi.org/10.1159/000064032
[28]
Guttridge, D.C., Albanese, C., Reuther, J.Y., Pestell, R.G. and Baldwin, A.S. (1999) NF-Kappa B Controls Cell Growth and Differentiation through Transcriptional Regulation of cyclinD1. Molecular and Cellular Biology, 19, 5785-5799.
[29]
La Rosa, F.A., Pierce, J.W. and Sonenshein, G.E. (1994) Differential Regulation of the c-myc Oncogene Promoter by the NF = Kb Rel Family of Transcription Factors. Molecular and Cellular Biology, 14, 1039-1044. https://doi.org/10.1128/MCB.14.2.1039
[30]
Dharmaraj, N., Wang, P. and Carson, D.D. (2010) Cytokine and Progesterone Receptor Interplay in the Regulation of MUC1 Gene Expression. Molecular Endocrinology, 24, 2253-2266. https://doi.org/10.1210/me.2009-0448
[31]
Wei, X., Xu, H. and Kufe, D. (2007) Human mucin1 Oncoprotein Represses Transcription of the p53 Tumor Suppressor Gene. Cancer Research, 67, 1853-1858. https://doi.org/10.1158/0008-5472.CAN-06-3063
[32]
Hollingsworth, M.A. and Swanson, B.J. (2004) Mucin in Cancer: Protection and Control of the Cell Surface. Nature Reviews Cancer, 4, 45-60. https://doi.org/10.1038/nrc1251
[33]
Ahmad, R., Alam, M., Rajabi, H. and Kufe, D. (2012) The MUC1-C Oncoprotein Binds to the BH3 Domain of the Pro Apoptotic Bax Protein and Blocks Bax Function. Biological Chemistry, 287, 20866-20875. https://doi.org/10.1074/jbc.M112.357293
[34]
Albrecht, H. and Carraway, K.L. (2011) MUC1 and MUC4: Switching the Emphasis from Large to Small. Cancer Biotherapy and Radiopharmaceuticals, 26, 261-271. https://doi.org/10.1089/cbr.2011.1017
[35]
Carrraway, K.L., Perez, A., Idris, N., et al. (2003) MUC4/Sialomucin Complex, the Intramembrane ErbB2 Ligand, in Cancer and Epithelia: To Protect and to Survive. Progress in Nucleic Acid Research and Molecular Biology, 71, 149-185. https://doi.org/10.1016/S0079-6603(02)71043-X
[36]
Jepson, S., Komatus, M., Haq, B., et al. (2002) MUC4/Sialomucin Complex, the Intramembrane ErbB2 Ligand, Induces Specific Phosphorylation of ErbB2 and Enhances Expression of P27(kip), But Does Not Activate Mitogen-Activated Kinase of Protein Kinase B/AKT Pathways. Oncogene, 21, 7524-7532. https://doi.org/10.1038/sj.onc.1205970
[37]
Bast, R. and Spriggs, D. (2011) More than a Biomarker; CA125 May Contribute to Ovarian Cancer Pathogenesis. Gynecologic Oncology, 121, 429-443. https://doi.org/10.1016/j.ygyno.2011.04.032
[38]
Felder, M., Kapur, A., Gonzalez-Bosquet, J., Horibata, S., Heintz, J., Albrecht, R., Fass, L., Kaur, J., Hu, K., Shojaei, H., Whelan, R. and Patankar, M. (2014) MUC16 (CA125): Tumor Biomarker to Cancer Therapy, a Work in Progress. Molecular Cancer, 13, 129. https://doi.org/10.1186/1476-4598-13-129
[39]
Li, Y.-F., Xu, X.-B., Chen, X.-H., Wei, G., He, B. and Wang, J.-D. (2010) The Nuclear Factor-kB Pathway Is Involved in Matrix Metalloproteinase-9 Expression in RU486-Induced Endometrium Breakdown in Mice. Human Reproduction, 27, 2096-2210.
[40]
Xie, T.-X., Xia, Z., Zhang, N., Gong, W. and Huang, S. (2010) Constitutive NF-Kappa B Activity Regulates the Expression of VEGF and IL-8 and Tumor Angiogenesis of Human Glioblastoma. Oncology Reports, 23, 725-732.
[41]
Van Lint, P. and Libert, C. (2007) Chemokine and Cytokine Processing by Matrix Metalloproteinases and Its Effect on Leukocyte Migration and Inflammation. Journal of Leukocyte Biology, 82, 1375-1381.
[42]
Lau, W., Ramagopal, U., Cheng, H., Bonanno, J.B., Toro, R., Bhosle, R., Zhan, C. and Almosc, S.C. (2016) Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DCR3. Structure, 24, 2016-2023. https://doi.org/10.1016/j.str.2016.09.009
[43]
Chen, P.H. and Yang, C.R. (2008) Decoy Receptor 3 Expression in AsPC-1 Human Pancreatic Adenocarcinoma Cells via the Phosphatidylinositol 3-kinase-, Akt-, and NF-kappa B-Dependent Pathway. The Journal of Immunology, 181, 8441-8449. https://doi.org/10.4049/jimmunol.181.12.8441
[44]
De Almodóvar, G.R., Ruiz, G.R., Rodríguez, A., Ortiz-Ferr ón, G., Redondo, J.M. and López-Rivas, A. (2003) TRAIL Decoy Receptor (TRAIL-R3) Is up Regulated by P53 in Breast Tumor Cell through a Mechanism Involving an Intronic P53 Binding Site.
