Role of p53, Cancer Stem Cells, and Cellular Senescence in Radiation Response

REVIEW
Juan C. Alamilla-Presuel

 
International Journal of Biomedicine. 2023;13(3):31-45.
DOI: 10.21103/Article13(3)_RA3
Originally published September 5, 2023

Abstract: 

Currently, radiotherapy has been identified as the most common cancer treatment. However, the efficacy of this treatment modality is low in several malignancies due to the resistance of cancer to radiation. Multiple mechanisms, including cell-cycle checkpoint function, DNA repair, and cell death pathways, modulate the radio-responsiveness of cancer cells. This review considered the role of p53, cancer stem cells (CSCs), and cellular senescence in radiation response.

Keywords: 
p53 • cancer stem cells • cellular senescence • radioresistance
References: 
  1. TP53 tumor protein p53 [Homo sapiens (human)] https://www.ncbi.nlm.nih.gov/gene/7157
  2. Lane DP. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15-6. doi: 10.1038/358015a0. 
  3. Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705-8. doi: 10.1038/342705a0. 
  4. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49-53. doi: 10.1126/science.1905840. 
  5. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer. 2002 Aug;2(8):594-604. doi: 10.1038/nrc864. 
  6. Joerger AC, Fersht AR. Structure-function-rescue: the diverse nature of common p53 cancer mutants. Oncogene. 2007 Apr 2;26(15):2226-42. doi: 10.1038/sj.onc.1210291.
  7. Chen PL, Chen YM, Bookstein R, Lee WH. Genetic mechanisms of tumor suppression by the human p53 gene. Science. 1990 Dec 14;250(4987):1576-80. doi: 10.1126/science.2274789.
  8. Ozaki T, Nakagawara A. Role of p53 in Cell Death and Human Cancers. Cancers (Basel). 2011 Mar 3;3(1):994-1013. doi: 10.3390/cancers3010994
  9. Strano S, Dell'Orso S, Di Agostino S, Fontemaggi G, Sacchi A, Blandino G. Mutant p53: an oncogenic transcription factor. Oncogene. 2007 Apr 2;26(15):2212-9. doi: 10.1038/sj.onc.1210296.
  10. Zhu G, Pan C, Bei JX, Li B, Liang C, Xu Y, Fu X. Mutant p53 in Cancer Progression and Targeted Therapies. Front Oncol. 2020 Nov 6;10:595187. doi: 10.3389/fonc.2020.595187.
  11. Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the Hallmarks of Cancer. Cancer Cell. 2018 Jul 9;34(1):21-43. doi: 10.1016/j.ccell.2018.03.022.
  12. Jeong Y, Hoang NT, Lovejoy A, Stehr H, Newman AM, Gentles AJ, Kong W, Truong D, Martin S, Chaudhuri A, Heiser D, Zhou L, Say C, Carter JN, Hiniker SM, Loo BW Jr, West RB, Beachy P, Alizadeh AA, Diehn M. Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance. Cancer Discov. 2017 Jan;7(1):86-101. doi: 10.1158/2159-8290.CD-16-0127. 
  13. Chee JL, Saidin S, Lane DP, Leong SM, Noll JE, Neilsen PM, Phua YT, Gabra H, Lim TM. Wild-type and mutant p53 mediate cisplatin resistance through interaction and inhibition of active caspase-9. Cell Cycle. 2013 Jan 15;12(2):278-88. doi: 10.4161/cc.23054. 
  14. Liu K, Ling S, Lin WC. TopBP1 mediates mutant p53 gain of function through NF-Y and p63/p73. Mol Cell Biol. 2011 Nov;31(22):4464-81. doi: 10.1128/MCB.05574-11. 
  15. Tchelebi L, Ashamalla H, Graves PR. Mutant p53 and the response to chemotherapy and radiation. Subcell Biochem. 2014;85:133-59. doi: 10.1007/978-94-017-9211-0_8. PMID: 25201193.
  16. Shetzer Y, Solomon H, Koifman G, Molchadsky A, Horesh S, Rotter V. The paradigm of mutant p53-expressing cancer stem cells and drug resistance. Carcinogenesis. 2014 Jun;35(6):1196-208. doi: 10.1093/carcin/bgu073
  17. Schulz A, Meyer F, Dubrovska A, Borgmann K. Cancer Stem Cells and Radioresistance: DNA Repair and Beyond. Cancers (Basel). 2019 Jun 21;11(6):862. doi: 10.3390/cancers11060862.
  18. Najafi M, Farhood B, Mortezaee K. Cancer stem cells (CSCs) in cancer progression and therapy. J Cell Physiol. 2019 Jun;234(6):8381-8395. doi: 10.1002/jcp.27740. 
  19. Olivos DJ, Mayo LD. Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness. Int J Mol Sci. 2016 Nov 26;17(12):1982. doi: 10.3390/ijms17121982.
  20. Krayem M, Sabbah M, Najem A, Wouters A, Lardon F, Simon S, Sales F, Journe F, Awada A, Ghanem GE, Van Gestel D. The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma. Cancers (Basel). 2019 Aug 1;11(8):1093. doi: 10.3390/cancers11081093. 
  21. Farhood B, Goradel NH, Mortezaee K, Khanlarkhani N, Salehi E, Nashtaei MS, Mirtavoos-Mahyari H, Motevaseli E, Shabeeb D, Musa AE, Najafi M. Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clin Transl Oncol. 2019 Mar;21(3):268-279. doi: 10.1007/s12094-018-1934-0. 
  22. Picca A, Lezza AM. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: Useful insights from aging and calorie restriction studies. Mitochondrion. 2015 Nov;25:67-75. doi: 10.1016/j.mito.2015.10.001.
  23. Hillen HS, Morozov YI, Sarfallah A, Temiakov D, Cramer P. Structural Basis of Mitochondrial Transcription Initiation. Cell. 2017 Nov 16;171(5):1072-1081.e10. doi: 10.1016/j.cell.2017.10.036.
  24. Ueta E, Sasabe E, Yang Z, Osaki T, Yamamoto T. Enhancement of apoptotic damage of squamous cell carcinoma cells by inhibition of the mitochondrial DNA repairing system. Cancer Sci. 2008 Nov;99(11):2230-7. doi: 10.1111/j.1349-7006.2008.00918.x. 
  25. Park JY, Wang PY, Matsumoto T, Sung HJ, Ma W, Choi JW, Anderson SA, Leary SC, Balaban RS, Kang JG, Hwang PM. p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res. 2009 Sep 25;105(7):705-12, 11 p following 712. doi: 10.1161/CIRCRESAHA.109.205310. 
  26. Wen S, Gao J, Zhang L, Zhou H, Fang D, Feng S. p53 increase mitochondrial copy number via up-regulation of mitochondrial transcription factor A in colorectal cancer. Oncotarget. 2016 Nov 15;7(46):75981-75995. doi: 10.18632/oncotarget.12514. 
  27. Yoshida Y, Izumi H, Torigoe T, Ishiguchi H, Itoh H, Kang D, Kohno K. P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA. Cancer Res. 2003 Jul 1;63(13):3729-34.
  28. He L, Lai H, Chen T. Dual-function nanosystem for synergetic cancer chemo-/radiotherapy through ROS-mediated signaling pathways. Biomaterials. 2015 May;51:30-42. doi: 10.1016/j.biomaterials.2015.01.063.
  29. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006 Jul 14;126(1):107-20. doi: 10.1016/j.cell.2006.05.036. 
  30. Bensaad K, Cheung EC, Vousden KH. Modulation of intracellular ROS levels by TIGAR controls autophagy. EMBO J. 2009 Oct 7;28(19):3015-26. doi: 10.1038/emboj.2009.242.
  31. Jiang X, Wang J. Down-regulation of TFAM increases the sensitivity of tumour cells to radiation via p53/TIGAR signalling pathway. J Cell Mol Med. 2019 Jul;23(7):4545-4558. doi: 10.1111/jcmm.14350. 
  32. Oshiro MM, Watts GS, Wozniak RJ, Junk DJ, Munoz-Rodriguez JL, Domann FE, Futscher BW. Mutant p53 and aberrant cytosine methylation cooperate to silence gene expression. Oncogene. 2003 Jun 5;22(23):3624-34. doi: 10.1038/sj.onc.1206545.
  33. Gomes NP, Espinosa JM. Gene-specific repression of the p53 target gene PUMA via intragenic CTCF-Cohesin binding. Genes Dev. 2010 May 15;24(10):1022-34. doi: 10.1101/gad.1881010. 
  34. Qu H, Su Y, Yu L, Zhao H, Xin C. Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer. FEBS Open Bio. 2018 Dec 20;9(1):26-34. doi: 10.1002/2211-5463.12554.
  35. Wu B, Wang H, Zhang L, Sun C, Li H, Jiang C, Liu X. High expression of RAD18 in glioma induces radiotherapy resistance via down-regulating P53 expression. Biomed Pharmacother. 2019 Apr;112:108555. doi: 10.1016/j.biopha.2019.01.016.
  36. Xie C, Wang H, Cheng H, Li J, Wang Z, Yue W. RAD18 mediates resistance to ionizing radiation in human glioma cells. Biochem Biophys Res Commun. 2014 Feb 28;445(1):263-8. doi: 10.1016/j.bbrc.2014.02.003. 
  37. Kunst HP, Rutten MH, de Mönnink JP, Hoefsloot LH, Timmers HJ, Marres HA, Jansen JC, Kremer H, Bayley JP, Cremers CW. SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin Cancer Res. 2011 Jan 15;17(2):247-54. doi: 10.1158/1078-0432.CCR-10-0420.
  38. Kaelin WG Jr. SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling. Cancer Cell. 2009 Sep 8;16(3):180-2. doi: 10.1016/j.ccr.2009.08.013. 
  39. Zong Y, Li Q, Zhang F, Xian X, Wang S, Xia J, Li J, Tuo Z, Xiao G, Liu L, Li G, Zhang S, Wu G, Liu J. SDH5 Depletion Enhances Radiosensitivity by Regulating p53: A New Method for Noninvasive Prediction of Radiotherapy Response. Theranostics. 2019 Aug 14;9(22):6380-6395. doi: 10.7150/thno.34443.
  40. Xie J, Li Y, Jiang K, Hu K, Zhang S, Dong X, Dai X, Liu L, Zhang T, Yang K, Huang K, Chen J, Shi S, Zhang Y, Wu G, Xu S. CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts Prognosis in Lung Cancer. Theranostics. 2018 Jan 1;8(3):650-662. doi: 10.7150/thno.21963.
  41. Malumbres M, Harlow E, Hunt T, Hunter T, Lahti JM, Manning G, Morgan DO, Tsai LH, Wolgemuth DJ. Cyclin-dependent kinases: a family portrait. Nat Cell Biol. 2009 Nov;11(11):1275-6. doi: 10.1038/ncb1109-1275.
  42. Yanagi T, Krajewska M, Matsuzawa S, Reed JC. PCTAIRE1 phosphorylates p27 and regulates mitosis in cancer cells. Cancer Res. 2014 Oct 15;74(20):5795-807. doi: 10.1158/0008-5472.CAN-14-0872. 
  43. Yanagi T, Matsuzawa S. PCTAIRE1/PCTK1/CDK16: a new oncotarget? Cell Cycle. 2015;14(4):463-4. doi: 10.1080/15384101.2015.1006539. 
  44. Yanagi T, Tachikawa K, Wilkie-Grantham R, Hishiki A, Nagai K, Toyonaga E, Chivukula P, Matsuzawa S. Lipid Nanoparticle-mediated siRNA Transfer Against PCTAIRE1/PCTK1/Cdk16 Inhibits In Vivo Cancer Growth. Mol Ther Nucleic Acids. 2016 Jun 28;5(6):e327. doi: 10.1038/mtna.2016.40.
  45. Rouse J, Jackson SP. Interfaces between the detection, signaling, and repair of DNA damage. Science. 2002 Jul 26;297(5581):547-51. doi: 10.1126/science.1074740. 
  46. Demetriou SK, Ona-Vu K, Sullivan EM, Dong TK, Hsu SW, Oh DH. Defective DNA repair and cell cycle arrest in cells expressing Merkel cell polyomavirus T antigen. Int J Cancer. 2012 Oct 15;131(8):1818-27. doi: 10.1002/ijc.27440. 
  47. Yang J, Jing L, Liu CJ, Bai WW, Zhu SC. 53BP1 regulates cell cycle arrest in esophageal cancer model. Eur Rev Med Pharmacol Sci. 2019 Jan;23(2):604-612. doi: 10.26355/eurrev_201901_16874. 
  48. Chen W, Liu Q, Fu B, Liu K, Jiang W. Overexpression of GRIM-19 accelerates radiation-induced osteosarcoma cells apoptosis by p53 stabilization. Life Sci. 2018 Sep 1;208:232-238. doi: 10.1016/j.lfs.2018.07.015.
  49. Yi H, Yan X, Luo Q, Yuan L, Li B, Pan W, Zhang L, Chen H, Wang J, Zhang Y, Zhai Y, Qiu MZ, Yang DJ. A novel small molecule inhibitor of MDM2-p53 (APG-115) enhances radiosensitivity of gastric adenocarcinoma. J Exp Clin Cancer Res. 2018 May 2;37(1):97. doi: 10.1186/s13046-018-0765-8. 
  50. Wang P, Sun W, Wang L, Gao J, Zhang J, He P. Correlations of p53 expression with transvaginal color Doppler ultrasound findings of cervical cancer after radiotherapy. J BUON. 2018 May-Jun;23(3):769-775. 
  51. Visconti R, Della Monica R, Grieco D. Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword. J Exp Clin Cancer Res. 2016 Sep 27;35(1):153. doi: 10.1186/s13046-016-0433-9. 
  52. Deckbar D, Jeggo PA, Löbrich M. Understanding the limitations of radiation-induced cell cycle checkpoints. Crit Rev Biochem Mol Biol. 2011 Aug;46(4):271-83. doi: 10.3109/10409238.2011.575764.
  53. Schmitt CA. Senescence, apoptosis and therapy--cutting the lifelines of cancer. Nat Rev Cancer. 2003 Apr;3(4):286-95. doi: 10.1038/nrc1044. 
  54. Gabrielli B, Brooks K, Pavey S. Defective cell cycle checkpoints as targets for anti-cancer therapies. Front Pharmacol. 2012 Feb 2;3:9. doi: 10.3389/fphar.2012.00009.
  55. Hematulin A, Sagan D, Sawanyawisuth K, Seubwai W, Wongkham S. Association between cellular radiosensitivity and G1/G2 checkpoint proficiencies in human cholangiocarcinoma cell lines. Int J Oncol. 2014 Sep;45(3):1159-66. doi: 10.3892/ijo.2014.2520.
  56. Koniaras K, Cuddihy AR, Christopoulos H, Hogg A, O'Connell MJ. Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells. Oncogene. 2001 Nov 8;20(51):7453-63. doi: 10.1038/sj.onc.1204942.
  57. Dillon MT, Good JS, Harrington KJ. Selective targeting of the G2/M cell cycle checkpoint to improve the therapeutic index of radiotherapy. Clin Oncol (R Coll Radiol). 2014 May;26(5):257-65. doi: 10.1016/j.clon.2014.01.009.
  58. Lee JM, Bernstein A. p53 mutations increase resistance to ionizing radiation. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5742-6. doi: 10.1073/pnas.90.12.5742.
  59. Hematulin A, Meethang S, Utapom K, Wongkham S, Sagan D. Etoposide radiosensitizes p53-defective cholangiocarcinoma cell lines independent of their G2 checkpoint efficacies. Oncol Lett. 2018 Mar;15(3):3895-3903. doi: 10.3892/ol.2018.7754. 
  60. Thakur DS. Topoisomerase II inhibitors in cancer Treatment. Int J Pharma Sci Nanotechnol. 2011;3:1173–1181.
  61. Groselj B, Sharma NL, Hamdy FC, Kerr M, Kiltie AE. Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair. Br J Cancer. 2013 Mar 5;108(4):748-54. doi: 10.1038/bjc.2013.21.
  62. Ree AH, Dueland S, Folkvord S, Hole KH, Seierstad T, Johansen M, Abrahamsen TW, Flatmark K. Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the Pelvic Radiation and Vorinostat (PRAVO) phase 1 study. Lancet Oncol. 2010 May;11(5):459-64. doi: 10.1016/S1470-2045(10)70058-9. 
  63. Chinnaiyan P, Cerna D, Burgan WE, Beam K, Williams ES, Camphausen K, Tofilon PJ. Postradiation sensitization of the histone deacetylase inhibitor valproic acid. Clin Cancer Res. 2008 Sep 1;14(17):5410-5. doi: 10.1158/1078-0432.CCR-08-0643. 
  64. Chen X, Wong P, Radany E, Wong JY. HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells. Cancer Biother Radiopharm. 2009 Dec;24(6):689-99. doi: 10.1089/cbr.2009.0629. 
  65. Terranova-Barberio M, Pecori B, Roca MS, Imbimbo S, Bruzzese F, Leone A, Muto P, Delrio P, Avallone A, Budillon A, Di Gennaro E. Synergistic antitumor interaction between valproic acid, capecitabine and radiotherapy in colorectal cancer: critical role of p53. J Exp Clin Cancer Res. 2017 Dec 6;36(1):177. doi: 10.1186/s13046-017-0647-5.
  66. Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 1995 Oct 12;377(6549):552-7. doi: 10.1038/377552a0.
  67. Choo DW, Goh SH, Cho YW, Baek HJ, Park EJ, Motoyama N, Kim TH, Kim JY, Kim SS. CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid. Oncol Lett. 2017 Apr;13(4):2591-2598. doi: 10.3892/ol.2017.5792.
  68. Shen YY, Yuan Y, Du YY, Pan YY. Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells. Mol Med Rep. 2015 Jul;12(1):623-30. doi: 10.3892/mmr.2015.3411.
  69. Hoque A, Chen H, Xu XC. Statin induces apoptosis and cell growth arrest in prostate cancer cells. Cancer Epidemiol Biomarkers Prev. 2008 Jan;17(1):88-94. doi: 10.1158/1055-9965.EPI-07-0531. 
  70. Hindler K, Cleeland CS, Rivera E, Collard CD. The role of statins in cancer therapy. Oncologist. 2006 Mar;11(3):306-15. doi: 10.1634/theoncologist.11-3-306. 
  71. Spampanato C, De Maria S, Sarnataro M, Giordano E, Zanfardino M, Baiano S, Cartenì M, Morelli F. Simvastatin inhibits cancer cell growth by inducing apoptosis correlated to activation of Bax and down-regulation of BCL-2 gene expression. Int J Oncol. 2012 Apr;40(4):935-41. doi: 10.3892/ijo.2011.1273.
  72. Lim T, Lee I, Kim J, Kang WK. Synergistic Effect of Simvastatin Plus Radiation in Gastric Cancer and Colorectal Cancer: Implications of BIRC5 and Connective Tissue Growth Factor. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):316-25. doi: 10.1016/j.ijrobp.2015.05.023.
  73. Lee JY, Kim MS, Ju JE, Lee MS, Chung N, Jeong YK. Simvastatin enhances the radiosensitivity of p53‑deficient cells via inhibition of mouse double minute 2 homolog. Int J Oncol. 2018 Jan;52(1):211-218. doi: 10.3892/ijo.2017.4192.
  74. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004 Feb 6;303(5659):844-8. doi: 10.1126/science.1092472.
  75. Yee-Lin V, Pooi-Fong W, Soo-Beng AK. Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment. Mini Rev Med Chem. 2018;18(2):173-183. doi: 10.2174/1389557517666170717125821.
  76. Faccion RS, Bernardo PS, de Lopes GPF, Bastos LS, Teixeira CL, de Oliveira JA, Fernandes PV, Dubois LG, Chimelli L, Maia RC. p53 expression and subcellular survivin localization improve the diagnosis and prognosis of patients with diffuse astrocytic tumors. Cell Oncol (Dordr). 2018 Apr;41(2):141-157. doi: 10.1007/s13402-017-0361-5. 
  77. Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem. 2002 Feb 1;277(5):3247-57. doi: 10.1074/jbc.M106643200.
  78. Mirza A, McGuirk M, Hockenberry TN, Wu Q, Ashar H, Black S, Wen SF, Wang L, Kirschmeier P, Bishop WR, Nielsen LL, Pickett CB, Liu S. Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene. 2002 Apr 18;21(17):2613-22. doi: 10.1038/sj.onc.1205353. 
  79. Stojanovic-Rundic S, Jankovic R, Micev M, Nikolic V, Popov I, Gavrilovic D, Plesinac-Karapandzic V, Djuric-Stefanovic A, Krivokapic Z, Radulovic S. p21 does, but p53 does not predict pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer. J BUON. 2017 Nov-Dec;22(6):1463-1470. 
  80. Mata-Miranda M, Vázquez-Sapién GJ, Sánchez-Monroy V. [Generalities and applications of the stem cells]. Perinatol Reprod Hum. 2013;27(3):194-9. [Article in Spanish].
  81. Alcalá-Pérez D. [Cancer stem cells: current concepts].  Rev Cent Dermatol Pascua. 2015; 24(2): 47-51. [Article in Spanish].
  82. Krause M, Yaromina A, Eicheler W, Koch U, Baumann M. Cancer stem cells: targets and potential biomarkers for radiotherapy. Clin Cancer Res. 2011 Dec 1;17(23):7224-9. doi: 10.1158/1078-0432
  83. de Araújo Farias V, O'Valle F, Lerma BA, Ruiz de Almodóvar C, López-Peñalver JJ, Nieto A, Santos A, Fernández BI, Guerra-Librero A, Ruiz-Ruiz MC, Guirado D, Schmidt T, Oliver FJ, Ruiz de Almodóvar JM. Human mesenchymal stem cells enhance the systemic effects of radiotherapy. Oncotarget. 2015 Oct 13;6(31):31164-80. doi: 10.18632/oncotarget.5216.
  84. Giuranno L, Wansleeben C, Iannone R, Arathoon L, Hounjet J, Groot AJ, Vooijs M. NOTCH signaling promotes the survival of irradiated basal airway stem cells. Am J Physiol Lung Cell Mol Physiol. 2019 Sep 1;317(3):L414-L423. doi: 10.1152/ajplung.00197.2019.
  85. Zamulaeva IA, Selivanova EI, Matchuk ON, Krikunova LI, Mkrtchyan LS, Kulieva GZ, Kaprin AD. Quantitative Changes in the Population of Cancer Stem Cells after Radiation Exposure in a Dose of 10 Gy as a Prognostic Marker of Immediate Results of the Treatment of Squamous Cell Cervical Cancer. Bull Exp Biol Med. 2019 Nov;168(1):156-159. doi: 10.1007/s10517-019-04667-x. 
  86. Chu K, Leonhardt EA, Trinh M, Prieur-Carrillo G, Lindqvist J, Albright N, Ling CC, Dewey WC. Computerized video time-lapse (CVTL) analysis of cell death kinetics in human bladder carcinoma cells (EJ30) X-irradiated in different phases of the cell cycle. Radiat Res. 2002 Dec;158(6):667-77. doi: 10.1667/0033-7587(2002)158[0667:cvtlca]2.0.co;2.
  87. Qiao L, Xu Z, Zhao T, Zhao Z, Shi M, Zhao RC, Ye L, Zhang X. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008 Apr;18(4):500-7. doi: 10.1038/cr.2008.40. 
  88. Li T, Song B, Du X, Wei Z, Huo T. Effect of bone-marrow-derived mesenchymal stem cells on high-potential hepatocellular carcinoma in mouse models: an intervention study. Eur J Med Res. 2013 Sep 30;18(1):34. doi: 10.1186/2047-783X-18-34. 
  89. Wu LW, Chen WL, Huang SM, Chan JY. Platelet-derived growth factor-AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing. FASEB J. 2019 Feb;33(2):2388-2395. doi: 10.1096/fj.201800658R. 
  90. Wu L, Tang Q, Yin X, Yan D, Tang M, Xin J, Pan Q, Ma C, Yan S. The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma. Front Cell Dev Biol. 2019 Nov 12;7:267. doi: 10.3389/fcell.2019.00267.
  91. Annett S, Robson T. Targeting cancer stem cells in the clinic: Current status and perspectives. Pharmacol Ther. 2018 Jul;187:13-30. doi: 10.1016/j.pharmthera.2018.02.001.
  92. Pützer BM, Solanki M, Herchenröder O. Advances in cancer stem cell targeting: How to strike the evil at its root. Adv Drug Deliv Rev. 2017 Oct 1;120:89-107. doi: 10.1016/j.addr.2017.07.013.
  93. Agliano A, Calvo A, Box C. The challenge of targeting cancer stem cells to halt metastasis. Semin Cancer Biol. 2017 Jun;44:25-42. doi: 10.1016/j.semcancer.2017.03.003. 
  94. Wu J, Ru NY, Zhang Y, Li Y, Wei D, Ren Z, Huang XF, Chen ZN, Bian H. HAb18G/CD147 promotes epithelial-mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug. Oncogene. 2011 Oct 27;30(43):4410-27. doi: 10.1038/onc.2011.149. 
  95. Tang J, Guo YS, Zhang Y, Yu XL, Li L, Huang W, Li Y, Chen B, Jiang JL, Chen ZN. CD147 induces UPR to inhibit apoptosis and chemosensitivity by increasing the transcription of Bip in hepatocellular carcinoma. Cell Death Differ. 2012 Nov;19(11):1779-90. doi: 10.1038/cdd.2012.60. 
  96. Wu J, Li Y, Dang YZ, Gao HX, Jiang JL, Chen ZN. HAb18G/CD147 promotes radioresistance in hepatocellular carcinoma cells: a potential role for integrin β1 signaling. Mol Cancer Ther. 2015 Feb;14(2):553-63. doi: 10.1158/1535-7163.MCT-14-0618.
  97. Xu J, Shen ZY, Chen XG, Zhang Q, Bian HJ, Zhu P, Xu HY, Song F, Yang XM, Mi L, Zhao QC, Tian R, Feng Q, Zhang SH, Li Y, Jiang JL, Li L, Yu XL, Zhang Z, Chen ZN. A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology. 2007 Feb;45(2):269-76. doi: 10.1002/hep.21465.
  98. Bian H, Zheng JS, Nan G, Li R, Chen C, Hu CX, Zhang Y, Sun B, Wang XL, Cui SC, Wu J, Xu J, Wei D, Zhang X, Liu H, Yang W, Ding Y, Li J, Chen ZN. Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation. J Natl Cancer Inst. 2014 Sep 10;106(9):dju239. doi: 10.1093/jnci/dju239.
  99. Fan XY, He D, Sheng CB, Wang B, Wang LJ, Wu XQ, Xu L, Jiang JL, Li L, Chen ZN. Therapeutic anti-CD147 antibody sensitizes cells to chemoradiotherapy via targeting pancreatic cancer stem cells. Am J Transl Res. 2019 Jun 15;11(6):3543-3554.
  100. Konířová J, Cupal L, Jarošová Š, Michaelidesová A, Vachelová J, Davídková M, Bartůněk P, Zíková M. Differentiation Induction as a Response to Irradiation in Neural Stem Cells In Vitro. Cancers (Basel). 2019 Jun 29;11(7):913. doi: 10.3390/cancers11070913. 
  101. Saha S, Aranda E, Hayakawa Y, Bhanja P, Atay S, Brodin NP, Li J, Asfaha S, Liu L, Tailor Y, Zhang J, Godwin AK, Tome WA, Wang TC, Guha C, Pollard JW. Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury. Nat Commun. 2016 Oct 13;7:13096. doi: 10.1038/ncomms13096.
  102. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012 Jun 8;149(6):1192-205. doi: 10.1016/j.cell.2012.05.012.
  103. Bhanja P, Norris A, Gupta-Saraf P, Hoover A, Saha S. BCN057 induces intestinal stem cell repair and mitigates radiation-induced intestinal injury. Stem Cell Res Ther. 2018 Feb 2;9(1):26. doi: 10.1186/s13287-017-0763-3.
  104. Wang Y, Probin V, Zhou D. Cancer therapy-induced residual bone marrow injury-Mechanisms of induction and implication for therapy. Curr Cancer Ther Rev. 2006 Aug 1;2(3):271-279. doi: 10.2174/157339406777934717. 
  105. Whelan TJ, Levine M, Julian J, Kirkbride P, Skingley P. The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomized trial. Ontario Clinical Oncology Group. Cancer. 2000 May 15;88(10):2260-6.
  106. Raghunathan D, Khilji MI, Hassan SA, Yusuf SW. Radiation-Induced Cardiovascular Disease. Curr Atheroscler Rep. 2017 May;19(5):22. doi: 10.1007/s11883-017-0658-x. 
  107. Bertók L. Radio-detoxified endotoxin activates natural immunity: a review. Pathophysiology. 2005 Sep;12(2):85-95. doi: 10.1016/j.pathophys.2005.02.004. 
  108. Bertok L, Berczi I. Nomenclature and significance of innate/natural immune mechanisms and species-specific resistance. Adv Neuroimmune Biol. 2011;1:11–24. doi: 10.3233/NIB-2011-002.
  109. Hegyesi H, Sándor N, Sáfrány G, Lovas V, Kovács Á, Takács A, Kőhidai L, Turiák L, Kittel Á, Pálóczi K, Bertók L, Buzás EI. Radio-detoxified LPS alters bone marrow-derived extracellular vesicles and endothelial progenitor cells. Stem Cell Res Ther. 2019 Oct 29;10(1):313. doi: 10.1186/s13287-019-1417-4. 
  110. Huen MS, Chen J. The DNA damage response pathways: at the crossroad of protein modifications. Cell Res. 2008 Jan;18(1):8-16. doi: 10.1038/cr.2007.109. 
  111. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998 Dec 17;396(6712):643-9. doi: 10.1038/25292. 
  112. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov 1;414(6859):105-11. doi: 10.1038/35102167. 
  113. Niwa O. Roles of stem cells in tissue turnover and radiation carcinogenesis. Radiat Res. 2010 Dec;174(6):833-9. doi: 10.1667/RR1970.1.
  114. Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008 Feb 22;132(4):681-96. doi: 10.1016/j.cell.2008.01.036. 
  115. Otsuka K, Iwasaki T. Effects of dose rates on radiation-induced replenishment of intestinal stem cells determined by Lgr5 lineage tracing. J Radiat Res. 2015 Jul;56(4):615-22. doi: 10.1093/jrr/rrv012.
  116. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009 Jan 29;457(7229):608-11. doi: 10.1038/nature07602.
  117. Otsuka K, Suzuki K, Fujimichi Y, Tomita M, Iwasaki T. Cellular responses and gene expression profiles of colonic Lgr5+ stem cells after low-dose/low-dose-rate radiation exposure. J Radiat Res. 2018 Apr 1;59(suppl_2):ii18-ii22. doi: 10.1093/jrr/rrx078.
  118. Brunner TB, Kunz-Schughart LA, Grosse-Gehling P, Baumann M. Cancer stem cells as a predictive factor in radiotherapy. Semin Radiat Oncol. 2012 Apr;22(2):151-74. doi: 10.1016/j.semradonc.2011.12.003.
  119. Morrison R, Schleicher SM, Sun Y, Niermann KJ, Kim S, Spratt DE, Chung CH, Lu B. Targeting the mechanisms of resistance to chemotherapy and radiotherapy with the cancer stem cell hypothesis. J Oncol. 2011;2011:941876. doi: 10.1155/2011/941876. 
  120. Pawlik TM, Keyomarsi K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):928-42. doi: 10.1016/j.ijrobp.2004.03.005. 
  121. Peitzsch C, Kurth I, Kunz-Schughart L, Baumann M, Dubrovska A. Discovery of the cancer stem cell related determinants of radioresistance. Radiother Oncol. 2013 Sep;108(3):378-87. doi: 10.1016/j.radonc.2013.06.003. 
  122. Metheetrairut C, Adams BD, Nallur S, Weidhaas JB, Slack FJ. cel-mir-237 and its homologue, hsa-miR-125b, modulate the cellular response to ionizing radiation. Oncogene. 2017 Jan 26;36(4):512-524. doi: 10.1038/onc.2016.222.
  123. Pajic M, Froio D, Daly S, Doculara L, Millar E, Graham PH, Drury A, Steinmann A, de Bock CE, Boulghourjian A, Zaratzian A, Carroll S, Toohey J, O'Toole SA, Harris AL, Buffa FM, Gee HE, Hollway GE, Molloy TJ. miR-139-5p Modulates Radiotherapy Resistance in Breast Cancer by Repressing Multiple Gene Networks of DNA Repair and ROS Defense. Cancer Res. 2018 Jan 15;78(2):501-515. doi: 10.1158/0008-5472.CAN-16-3105.
  124. Fabris L, Berton S, Citron F, D'Andrea S, Segatto I, Nicoloso MS, Massarut S, Armenia J, Zafarana G, Rossi S, Ivan C, Perin T, Vaidya JS, Avanzo M, Roncadin M, Schiappacassi M, Bristow RG, Calin G, Baldassarre G, Belletti B. Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway. Oncogene. 2016 Sep 15;35(37):4914-26. doi: 10.1038/onc.2016.23.
  125. Wilke CM, Hess J, Klymenko SV, Chumak VV, Zakhartseva LM, Bakhanova EV, Feuchtinger A, Walch AK, Selmansberger M, Braselmann H, Schneider L, Pitea A, Steinhilber J, Fend F, Bösmüller HC, Zitzelsberger H, Unger K. Expression of miRNA-26b-5p and its target TRPS1 is associated with radiation exposure in post-Chernobyl breast cancer. Int J Cancer. 2018 Feb 1;142(3):573-583. doi: 10.1002/ijc.31072.
  126. Griñán-Lisón C, Olivares-Urbano MA, Jiménez G, López-Ruiz E, Del Val C, Morata-Tarifa C, Entrena JM, González-Ramírez AR, Boulaiz H, Zurita Herrera M, Núñez MI, Marchal JA. miRNAs as radio-response biomarkers for breast cancer stem cells. Mol Oncol. 2020 Mar;14(3):556-570. doi: 10.1002/1878-0261.12635. 
  127. Tekade RK, Sun X. The Warburg effect and glucose-derived cancer theranostics. Drug Discov Today. 2017 Nov;22(11):1637-1653. doi: 10.1016/j.drudis.2017.08.003.
  128. Zhong JT, Zhou SH. Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma. Oncotarget. 2017 Feb 21;8(8):14133-14146. doi: 10.18632/oncotarget.13044. 
  129. Pitroda SP, Wakim BT, Sood RF, Beveridge MG, Beckett MA, MacDermed DM, Weichselbaum RR, Khodarev NN. STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect. BMC Med. 2009 Nov 5;7:68. doi: 10.1186/1741-7015-7-68. 
  130. Harada H. Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance. J Radiat Res. 2016 Aug;57 Suppl 1(Suppl 1):i99-i105. doi: 10.1093/jrr/rrw012.
  131. Zhang TB, Zhao Y, Tong ZX, Guan YF. Inhibition of glucose-transporter 1 (GLUT-1) expression reversed Warburg effect in gastric cancer cell MKN45. Int J Clin Exp Med. 2015 Feb 15;8(2):2423-8.
  132. Luo XM, Xu B, Zhou ML, Bao YY, Zhou SH, Fan J, Lu ZJ. Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo. PLoS One. 2015 Nov 24;10(11):e0143306. doi: 10.1371/journal.pone.0143306. 
  133. Shen LF, Zhao X, Zhou SH, Lu ZJ, Zhao K, Fan J, Zhou ML. In vivo evaluation of the effects of simultaneous inhibition of GLUT-1 and HIF-1α by antisense oligodeoxynucleotides on the radiosensitivity of laryngeal carcinoma using micro 18F-FDG PET/CT. Oncotarget. 2017 May 23;8(21):34709-34726. doi: 10.18632/oncotarget.16671.
  134. Bao YY, Zhou SH, Lu ZJ, Fan J, Huang YP. Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo. Oncol Rep. 2015 Oct;34(4):1805-14. doi: 10.3892/or.2015.4158. 
  135. Jiang T, Zhou ML, Fan J. Inhibition of GLUT-1 expression and the PI3K/Akt pathway to enhance the chemosensitivity of laryngeal carcinoma cells in vitro. Onco Targets Ther. 2018 Nov 6;11:7865-7872. doi: 10.2147/OTT.S176818. 
  136. Zhong JT, Yu Q, Zhou SH, Yu E, Bao YY, Lu ZJ, Fan J. GLUT-1 siRNA Enhances Radiosensitization Of Laryngeal Cancer Stem Cells Via Enhanced DNA Damage, Cell Cycle Redistribution, And Promotion Of Apoptosis In Vitro And In Vivo. Onco Targets Ther. 2019 Nov 5;12:9129-9142. doi: 10.2147/OTT.S221423. 
  137. Chowdhury M, Mihara K, Yasunaga S, Ohtaki M, Takihara Y, Kimura A. Expression of Polycomb-group (PcG) protein BMI-1 predicts prognosis in patients with acute myeloid leukemia. Leukemia. 2007 May;21(5):1116-22. doi: 10.1038/sj.leu.2404623
  138. Vonlanthen S, Heighway J, Altermatt HJ, Gugger M, Kappeler A, Borner MM, van Lohuizen M, Betticher DC. The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer. 2001 May 18;84(10):1372-6. doi: 10.1054/bjoc.2001.1791.
  139. Zhang FB, Sui LH, Xin T. Correlation of Bmi-1 expression and telomerase activity in human ovarian cancer. Br J Biomed Sci. 2008;65(4):172-7. doi: 10.1080/09674845.2008.11732824. 
  140. Song LB, Li J, Liao WT, Feng Y, Yu CP, Hu LJ, Kong QL, Xu LH, Zhang X, Liu WL, Li MZ, Zhang L, Kang TB, Fu LW, Huang WL, Xia YF, Tsao SW, Li M, Band V, Band H, Shi QH, Zeng YX, Zeng MS. The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells. J Clin Invest. 2009 Dec;119(12):3626-36. doi: 10.1172/JCI39374. 
  141. Ye L, Wang C, Yu G, Jiang Y, Sun D, Zhang Z, Yu X, Li X, Wei W, Liu P, Cheng J, DU B, Hu L. Bmi-1 induces radioresistance by suppressing senescence in human U87 glioma cells. Oncol Lett. 2014 Dec;8(6):2601-2606. doi: 10.3892/ol.2014.2606. 
  142. Bruggeman SW, Hulsman D, Tanger E, Buckle T, Blom M, Zevenhoven J, van Tellingen O, van Lohuizen M. Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell. 2007 Oct;12(4):328-41. doi: 10.1016/j.ccr.2007.08.032. 
  143. Wu C, Sun M, Liu L, Zhou GW. The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene. 2003 Mar 13;306:1-12. doi: 10.1016/s0378-1119(03)00400-1.
  144. Evren S, Wan S, Ma XZ, Fahim S, Mody N, Sakac D, Jin T, Branch DR. Characterization of SHP-1 protein tyrosine phosphatase transcripts, protein isoforms and phosphatase activity in epithelial cancer cells. Genomics. 2013 Nov-Dec;102(5-6):491-9. doi: 10.1016/j.ygeno.2013.10.001. 
  145. Amin S, Kumar A, Nilchi L, Wright K, Kozlowski M. Breast cancer cells proliferation is regulated by tyrosine phosphatase SHP1 through c-jun N-terminal kinase and cooperative induction of RFX-1 and AP-4 transcription factors. Mol Cancer Res. 2011 Aug;9(8):1112-25. doi: 10.1158/1541-7786.MCR-11-0097. 
  146. Sun Z, Pan X, Zou Z, Ding Q, Wu G, Peng G. Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells. Radiat Oncol. 2015 Jul 28;10:152. doi: 10.1186/s13014-015-0445-1. 
  147. Sabin RJ, Anderson RM. Cellular Senescence - its role in cancer and the response to ionizing radiation. Genome Integr. 2011 Aug 11;2(1):7. doi: 10.1186/2041-9414-2-7. 
  148. Coppé JP, Kauser K, Campisi J, Beauséjour CM. Secretion of vascular endothelial growth factor by primary human fibroblasts at senescence. J Biol Chem. 2006 Oct 6;281(40):29568-74. doi: 10.1074/jbc.M603307200. 
  149. Coppé JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010;5:99-118. doi: 10.1146/annurev-pathol-121808-102144. 
  150. Kumari R, Jat P. Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype. Front Cell Dev Biol. 2021 Mar 29;9:645593. doi: 10.3389/fcell.2021.645593.
  151. Birch J, Gil J. Senescence and the SASP: many therapeutic avenues. Genes Dev. 2020 Dec 1;34(23-24):1565-1576. doi: 10.1101/gad.343129.120. 
  152. Wang L, Lankhorst L, Bernards R. Exploiting senescence for the treatment of cancer. Nat Rev Cancer. 2022 Jun;22(6):340-355. doi: 10.1038/s41568-022-00450-9. 
  153. Chen Z, Cao K, Xia Y, Li Y, Hou Y, Wang L, Li L, Chang L, Li W. Cellular senescence in ionizing radiation (Review). Oncol Rep. 2019 Sep;42(3):883-894. doi: 10.3892/or.2019.7209.
  154. Patel NH, Sohal SS, Manjili MH, Harrell JC, Gewirtz DA. The Roles of Autophagy and Senescence in the Tumor Cell Response to Radiation. Radiat Res. 2020 Aug 1;194(2):103-115. doi: 10.1667/RADE-20-00009. 
  155. Rodier F, Coppé JP, Patil CK, Hoeijmakers WA, Muñoz DP, Raza SR, Freund A, Campeau E, Davalos AR, Campisi J. Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009 Aug;11(8):973-9. doi: 10.1038/ncb1909. Epub 2009 Jul 13. Erratum in: Nat Cell Biol. 2009 Oct;11(10):1272. Dosage error in article text. PMID: 19597488; PMCID: PMC2743561.
  156. Suzuki M, Boothman DA. Stress-induced premature senescence (SIPS)--influence of SIPS on radiotherapy. J Radiat Res. 2008 Mar;49(2):105-12. doi: 10.1269/jrr.07081.
  157. Raffetto JD, Leverkus M, Park HY, Menzoian JO. Synopsis on cellular senescence and apoptosis. J Vasc Surg. 2001 Jul;34(1):173-7. doi: 10.1067/mva.2001.
  158. Tsai KK, Stuart J, Chuang YY, Little JB, Yuan ZM. Low-dose radiation-induced senescent stromal fibroblasts render nearby breast cancer cells radioresistant. Radiat Res. 2009 Sep;172(3):306-13. doi: 10.1667/RR1764.1. 
  159. Mirzayans R, Scott A, Cameron M, Murray D. Induction of accelerated senescence by gamma radiation in human solid tumor-derived cell lines expressing wild-type TP53. Radiat Res. 2005 Jan;163(1):53-62. doi: 10.1667/rr3280.
  160. Yu X, Liu Y, Yin L, Peng Y, Peng Y, Gao Y, Yuan B, Zhu Q, Cao T, Xie B, Sun L, Chen Y, Gong Z, Qiu Y, Fan X, Li X. Radiation-promoted CDC6 protein stability contributes to radioresistance by regulating senescence and epithelial to mesenchymal transition. Oncogene. 2019 Jan;38(4):549-563. doi: 10.1038/s41388-018-0460-4.
  161. Borlado LR, Méndez J. CDC6: from DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis. 2008 Feb;29(2):237-43. doi: 10.1093/carcin/bgm268.
  162. Liu Y, Hock JM, Van Beneden RJ, Li X. Aberrant overexpression of FOXM1 transcription factor plays a critical role in lung carcinogenesis induced by low doses of arsenic. Mol Carcinog. 2014 May;53(5):380-91. doi: 10.1002/mc.21989.
  163. Young A, Berry R, Holloway AF, Blackburn NB, Dickinson JL, Skala M, Phillips JL, Brettingham-Moore KH. RNA-seq profiling of a radiation resistant and radiation sensitive prostate cancer cell line highlights opposing regulation of DNA repair and targets for radiosensitization. BMC Cancer. 2014 Nov 4;14:808. doi: 10.1186/1471-2407-14-
  164. Kastenhuber ER, Lowe SW. Putting p53 in Context. Cell. 2017 Sep 7;170(6):1062-1078. doi: 10.1016/j.cell.2017.08.028.
  165. Fischer M. Census and evaluation of p53 target genes. Oncogene. 2017 Jul 13;36(28):3943-3956. doi: 10.1038/onc.2016.502.
  166. Williams AB, Schumacher B. p53 in the DNA-Damage-Repair Process. Cold Spring Harb Perspect Med. 2016 May 2;6(5):a026070. doi: 10.1101/cshperspect.a026070. 
  167. He Q, Au B, Kulkarni M, Shen Y, Lim KJ, Maimaiti J, Wong CK, Luijten MNH, Chong HC, Lim EH, Rancati G, Sinha I, Fu Z, Wang X, Connolly JE, Crasta KC. Chromosomal instability-induced senescence potentiates cell non-autonomous tumourigenic effects. Oncogenesis. 2018 Aug 15;7(8):62. doi: 10.1038/s41389-018-0072-4. 

Download Article
Received June 16, 2023.
Accepted August 21, 2023.
©2023 International Medical Research and Development Corporation.