MOLECULAR MECHANISMS UNDERLYING CANCER CELL RADIORESISTANCE
Keywords:
ionizing radiation, DNA repair, cell cycle, proliferation, radiotherapy
Abstract
Radioresistance of the tumor cells remains a significant obstacle for the radiotherapy treatment of cancer. Radioresistance involves multiple genes, factors, and mechanisms that adapt cancer cells or tissues to radiotherapy-induced changes and develop resistance to ionizing radiation. The major studies of the effect of radiation on cells reported include the following areas: 1) the study of DNA damages and their repair; 2) mutations in tumor suppressor genes and radiation-induced oncogene expression; 3) the role of growth factors and cytokines; 4) violation of the cell cycle; 5) elucidation of the mechanisms of apoptosis and necrosis. This review aimed to provide a theoretical basis, which may improve the sensitivity of cancer cells to radiotherapy. It focuses on the roles of tumor metabolism, DNA repair capacity, cell cycle checkpoints, and the tumor microenvironment in the development of radioresistance of cancer cells. Understanding the molecular alterations that lead to radioresistance may provide new diagnostic markers and therapeutic targets to improve radiotherapy efficacy.
References
1. Al Bitar, S., & Gali-Muhtasib, H. (2019). The Role of the Cyclin Dependent Kinase Inhibitor p21cip1/waf1 in Targeting Cancer: Molecular Mechanisms and Novel Therapeutics. Cancers, 11(10), 1475. https://doi.org/10.3390/cancers11101475
2. Bakkenist, C. J., & Kastan, M. B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature, 421(6922), 499–506. https://doi.org/10.1038/nature01368
3. Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: back to Virchow?. Lancet (London, England), 357(9255), 539–545. https://doi.org/10.1016/S0140-6736(00)04046-0
4. Bencokova, Z., Kaufmann, M. R., Pires, I. M., Lecane, P. S., Giaccia, A. J., & Hammond, E. M. (2009). ATM activation and signaling under hypoxic conditions. Molecular and cellular biology, 29(2), 526–537. https://doi.org/10.1128/MCB.01301-08
5. Bhatt, A. N., Chauhan, A., Khanna, S., Rai, Y., Singh, S., Soni, R., Kalra, N., & Dwarakanath, B. S. (2015). Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells. BMC cancer, 15, 335. https://doi.org/10.1186/s12885-015-1368-9
6. Brandsma, I., & Gent, D. C. (2012). Pathway choice in DNA double strand break repair: observations of a balancing act. Genome integrity, 3(1), 9. https://doi.org/10.1186/2041-9414-3-9
7. Brown, J. M., Recht, L., & Strober, S. (2017). The Promise of Targeting Macrophages in Cancer Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 23(13), 3241–3250. https://doi.org/10.1158/1078-0432.CCR-16-3122
8. Buscemi, G., Savio, C., Zannini, L., Miccichè, F., Masnada, D., Nakanishi, M., Tauchi, H., Komatsu, K., Mizutani, S., Khanna, K., Chen, P., Concannon, P., Chessa, L., & Delia, D. (2001). Chk2 activation dependence on Nbs1 after DNA damage. Molecular and cellular biology, 21(15), 5214–5222. https://doi.org/10.1128/MCB.21.15.5214-5222.2001
9. Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000). Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes & development, 14(3), 278–288.
10. Chen, Y., Li, Z., Dong, Z., Beebe, J., Yang, K., Fu, L., & Zhang, J. T. (2017). 14-3-3σ Contributes to Radioresistance By Regulating DNA Repair and Cell Cycle via PARP1 and CHK2. Molecular cancer research : MCR, 15(4), 418–428. https://doi.org/10.1158/1541-7786.MCR-16-0366
11. Chevalier, F., Hamdi, D. H., Saintigny, Y., & Lefaix, J. L. (2015). Proteomic overview and perspectives of the radiation-induced bystander effects. Mutation research. Reviews in mutation research, 763, 280–293. https://doi.org/10.1016/j.mrrev.2014.11.008
12. Chu, T. Y., Yang, J. T., Huang, T. H., & Liu, H. W. (2014). Crosstalk with cancer-associated fibroblasts increases the growth and radiation survival of cervical cancer cells. Radiation research, 181(5), 540–547. https://doi.org/10.1667/RR13583.1
13. Chung, F. Y., Huang, M. Y., Yeh, C. S., Chang, H. J., Cheng, T. L., Yen, L. C., Wang, J. Y. & Lin, S. R. (2009). GLUT1 gene is a potential hypoxic marker in colorectal cancer patients. BMC Cancer, 9, 241. https://doi.org/10.1186/1471-2407-9-241
14. Cook, P. J., Thomas, R., Kingsley, P. J., Shimizu, F., Montrose, D. C., Marnett, L. J., Tabar, V. S., Dannenberg, A. J., & Benezra, R. (2016). Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma. Neuro-oncology, 18(10), 1379–1389. https://doi.org/10.1093/neuonc/now049
15. Dasika, G. K., Lin, S. C., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y. (1999). DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 18(55), 7883–7899. https://doi.org/10.1038/sj.onc.1203283
16. De Schutter, H., Landuyt, W., Verbeken, E., Goethals, L., Hermans, R., & Nuyts, S. (2005). The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +/- chemotherapy. BMC cancer, 5, 42. https://doi.org/10.1186/1471-2407-5-42
17. Dehne, N., Mora, J., Namgaladze, D., Weigert, A., & Brüne, B. (2017). Cancer cell and macrophage cross-talk in the tumor microenvironment. Current opinion in pharmacology, 35, 12–19. https://doi.org/10.1016/j.coph.2017.04.007
18. Erenpreisa, J., Cragg, M. S. (2001). Mitotic death: a mechanism of survival? A review. Cancer Cell International, 1(1), 1–7. https://doi.org/10.1186/1475-2867-1-1
19. Falcicchio, M., Ward, J. A., Macip, S. & Doveston, R. G. (2020). Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer. Cell Death Discovery, 6, 126. https://doi.org/10.1038/s41420-020-00362-3
20. Falck, J., Petrini, J. H., Williams, B. R., Lukas, J., & Bartek, J. (2002). The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nature genetics, 30(3), 290–294. https://doi.org/10.1038/ng845
21. Fang, J., Zhou, S. H., Fan, J., & Yan, S. X. (2015). Roles of glucose transporter-1 and the phosphatidylinositol 3‑kinase/protein kinase B pathway in cancer radioresistance (review). Molecular medicine reports, 11(3), 1573–1581. https://doi.org/10.3892/mmr.2014.2888
22. Frankenberg-Schwager, M., Gebauer, A., Koppe, C., Wolf, H., Pralle, E., & Frankenberg, D. (2009). Single-strand annealing, conservative homologous recombination, nonhomologous DNA end joining, and the cell cycle-dependent repair of DNA double-strand breaks induced by sparsely or densely ionizing radiation. Radiation research, 171(3), 265–273. https://doi.org/10.1667/RR0784.1
23. Gatei, M., Scott, S. P., Filippovitch, I., Soronika, N., Lavin, M. F., Weber, B., & Khanna, K. K. (2000). Role for ATM in DNA damage-induced phosphorylation of BRCA1. Cancer research, 60(12), 3299–3304.
24. Goffart, N., Lombard, A., Lallemand, F., Kroonen, J., Nassen, J., Di Valentin, E., Berendsen, S., Dedobbeleer, M., Willems, E., Robe, P., Bours, V., Martin, D., Martinive, P., Maquet, P., & Rogister, B. (2017). CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. Neuro-oncology, 19(1), 66–77. https://doi.org/10.1093/neuonc/now136
25. Gorodetska, I., Kozeretska, I., & Dubrovska, A. (2019). BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. Journal of Cancer, 10(9), 2109–2127. https://doi.org/10.7150/jca.30410
26. Harada H. (2011). How can we overcome tumor hypoxia in radiation therapy?. Journal of radiation research, 52(5), 545–556. https://doi.org/10.1269/jrr.11056
27. Harada H. (2016). Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance. Journal of radiation research, 57 Suppl 1(Suppl 1), i99–i105. https://doi.org/10.1093/jrr/rrw012
28. Hashimoto, T., Murata, Y., Urushihara, Y., Shiga, S., Takeda, K., & Hosoi, Y. (2018). Severe hypoxia increases expression of ATM and DNA-PKcs and it increases their activities through Src and AMPK signaling pathways. Biochemical and biophysical research communications, 505(1), 13–19. https://doi.org/10.1016/j.bbrc.2018.09.068
29. Her, J., & Bunting, S. F. (2018). How cells ensure correct repair of DNA double-strand breaks. The Journal of biological chemistry, 293(27), 10502–10511. https://doi.org/10.1074/jbc.TM118.000371
30. Huang, R. X., Zhou, P. K. (2020). DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduction and Targeted Therapy, 5, 60. https://doi.org/10.1038/s41392-020-0150-x
31. Jasin, M., & Rothstein, R. (2013). Repair of strand breaks by homologous recombination. Cold Spring Harbor perspectives in biology, 5(11), a012740. https://doi.org/10.1101/cshperspect.a012740
32. Javle, M., & Curtin, N. J. (2011). The role of PARP in DNA repair and its therapeutic exploitation. British journal of cancer, 105(8), 1114–1122. https://doi.org/10.1038/bjc.2011.382
33. Kastan, M. B., Lim, D. S., Kim, S. T., & Yang, D. (2001). ATM--a key determinant of multiple cellular responses to irradiation. Acta oncologica (Stockholm, Sweden), 40(6), 686–688. https://doi.org/10.1080/02841860152619089
34. Khanna, K. K., Keating, K. E., Kozlov, S., Scott, S., Gatei, M., Hobson, K., Taya, Y., Gabrielli, B., Chan, D., Lees-Miller, S. P., & Lavin, M. F. (1998). ATM associates with and phosphorylates p53: mapping the region of interaction. Nature genetics, 20(4), 398–400. https://doi.org/10.1038/3882
35. Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y., & Shkedy, D. (1999). Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America, 96(26), 14973–14977. https://doi.org/10.1073/pnas.96.26.14973
36. Krisnawan, V. E., Stanley, J. A., Schwarz, J. K., & DeNardo, D. G. (2020). Tumor Microenvironment as a Regulator of Radiation Therapy: New Insights into Stromal-Mediated Radioresistance. Cancers, 12(10), 2916. https://doi.org/10.3390/cancers12102916
37. Kunkel, M., Moergel, M., Stockinger, M., Jeong, J. H., Fritz, G., Lehr, H. A., & Whiteside, T. L. (2007). Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral oncology, 43(8), 796–803. https://doi.org/10.1016/j.oraloncology.2006.10.009
38. Lee, C. W., & La Thangue, N. B. (1999). Promoter specificity and stability control of the p53-related protein p73. Oncogene, 18(29), 4171–4181. https://doi.org/10.1038/sj.onc.1202793
39. Li, F., Zhou, K., Gao, L., Zhang, B., Li, W., Yan, W., Song, X., Yu, H., Wang, S., Yu, N., & Jiang, Q. (2016). Radiation induces the generation of cancer stem cells: A novel mechanism for cancer radioresistance. Oncology letters, 12(5), 3059–3065. https://doi.org/10.3892/ol.2016.5124
40. Liu, Y-P., Zheng, C-C., Huang, Y-N., Xu, W. W , Li, B. (2021). Molecular mechanisms of chemoand radiotherapy resistance and the potential implications for cancer treatment. MedComm, 2(3), 315–340. https://doi.org/10.1002/mco2.55
41. Mao, Z., Bozzella, M., Seluanov, A., & Gorbunova, V. (2008). Comparison of nonhomologous end joining and homologous recombination in human cells. DNA repair, 7(10), 1765–1771. https://doi.org/10.1016/j.dnarep.2008.06.018
42. Marsden, C. G., Dragon, J. A., Wallace, S. S., & Sweasy, J. B. (2017). Base Excision Repair Variants in Cancer. Methods in enzymology, 591, 119–157. https://doi.org/10.1016/bs.mie.2017.03.003
43. Maya, R., Balass, M., Kim, S. T., Shkedy, D., Leal, J. F., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., Kastan, M. B., Katzir, E., & Oren, M. (2001). ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes & development, 15(9), 1067–1077. https://doi.org/10.1101/gad.886901
44. Meijer, T. W., Kaanders, J. H., Span, P. N., & Bussink, J. (2012). Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clinical cancer research : an official journal of the American Association for Cancer Research, 18(20), 5585–5594. https://doi.org/10.1158/1078-0432.CCR-12-0858
45. Meng, Y., Beckett, M. A., Liang, H., Mauceri, H. J., van Rooijen, N., Cohen, K. S., & Weichselbaum, R. R. (2010). Blockade of tumor necrosis factor alpha signaling in tumor-associated macrophages as a radiosensitizing strategy. Cancer research, 70(4), 1534–1543. https://doi.org/10.1158/0008-5472.CAN-09-2995
46. Mladenov, E., & Iliakis, G. (2011). Induction and repair of DNA double strand breaks: the increasing spectrum of non-homologous end joining pathways. Mutation research, 711(1-2), 61–72. https://doi.org/10.1016/j.mrfmmm.2011.02.005
47. Morgan, M. A., & Lawrence, T. S. (2015). Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways. Clinical cancer research : an official journal of the American Association for Cancer Research, 21(13), 2898–2904. https://doi.org/10.1158/1078-0432.CCR-13-3229
48. Moureau, S., Luessing, J., Harte, E. C., Voisin, M., & Lowndes, N. F. (2016). A role for the p53
49. tumour suppressor in regulating the balance between homologous recombination and non-homologous end joining. Open biology, 6(9), 160225. https://doi.org/10.1098/rsob.160225
50. Nakashima, R., Goto, Y., Koyasu, S., Kobayashi, M., Morinibu, A., Yoshimura, M., Hiraoka, M., Hammond, E. M., & Harada, H. (2017). UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization. Scientific reports, 7(1), 6879. https://doi.org/10.1038/s41598-017-06605-1
51. O'Connell, M. J., Walworth, N. C., & Carr, A. M. (2000). The G2-phase DNA-damage checkpoint. Trends in cell biology, 10(7), 296–303. https://doi.org/10.1016/s0962-8924(00)01773-6
52. Olcina, M. M., Grand, R. J., & Hammond, E. M. (2014). ATM activation in hypoxia – causes and consequences. Molecular & cellular oncology, 1(1), e29903. https://doi.org/10.4161/mco.29903
53. Patra, K. C., & Hay, N. (2014). The pentose phosphate pathway and cancer. Trends in biochemical sciences, 39(8), 347–354. https://doi.org/10.1016/j.tibs.2014.06.005
54. Sharma, A., Singh, K., & Almasan, A. (2012). Histone H2AX phosphorylation: a marker for DNA damage. Methods in molecular biology (Clifton, N.J.), 920, 613–626. https://doi.org/10.1007/978-1-61779-998-3_40
55. Shu, K. X., Li, B., & Wu, L. X. (2007). The p53 network: p53 and its downstream genes. Colloids and surfaces. B, Biointerfaces, 55(1), 10–18. https://doi.org/10.1016/j.colsurfb.2006.11.003 Sia, J., Szmyd, R., Hau, E., & Gee, H. E. (2020). Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer. Frontiers in cell and developmental biology, 8, 41. https://doi.org/10.3389/fcell.2020.00041
56. Suwa, T., Kobayashi, M., Nam, J. M., Harada H. (2021). Tumor microenvironment and radioresistance. Experimental & molecular medicine, 53, 1029–1035. https://doi.org/10.1038/s12276-021-00640-9
57. Suzuki, K., Mori, I., Nakayama, Y., Miyakoda, M., Kodama, S., & Watanabe, M. (2001). Radiation-induced senescence-like growth arrest requires TP53 function but not telomere shortening. Radiation research, 155(1 Pt 2), 248–253. https://doi.org/10.1667/0033-7587(2001)155 [0248:rislga]2.0.co;2
58. Suzuki, K., Yokoyama, S., Waseda, S., Kodama, S., & Watanabe, M. (2003). Delayed reactivation of p53 in the progeny of cells surviving ionizing radiation. Cancer research, 63(5), 936–941.
59. Tang, L., Wei, F., Wu, Y., He, Y., Shi, L., Xiong, F., Gong, Z., Guo, C., Li, X., Deng, H., Cao, K., Zhou, M., Xiang, B., Li, X., Li, Y., Li, G., Xiong, W., & Zeng, Z. (2018). Role of metabolism in cancer cell radioresistance and radiosensitization methods. Journal of experimental & clinical cancer research : CR, 37(1), 87. https://doi.org/10.1186/s13046-018-0758-7
60. Tang, Y., He, Y., Shi, L., Yang, L., Wang, J., Lian, Y., Fan, C., Zhang, P., Guo, C., Zhang, S., Gong, Z., Li, X., Xiong, F., Li, X., Li, Y., Li, G., Xiong, W., & Zeng, Z. (2017). Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma. Oncotarget, 8(24), 39001–39011. https://doi.org/10.18632/oncotarget.16545
61. Telarovic, I., Wenger, R. H. & Pruschy, M. (2021). Interfering with Tumor Hypoxia for Radiotherapy Optimization. Journal of experimental & clinical cancer research : CR, 40 (1), 197. https://doi.org/10.1186/s13046-021-02000-x
62. Velegzhaninov, I. O., Belykh, E. S., Rasova, E. E., Pylina, Y. I., Shadrin, D. M., & Klokov, D. Y. (2020). Radioresistance, DNA Damage and DNA Repair in Cells With Moderate Overexpression of RPA1. Frontiers in genetics, 11, 855. https://doi.org/10.3389/fgene.2020.00855
63. Vítor, A. C., Huertas, P., Legube, G., & de Almeida, S. F. (2020). Studying DNA Double-Strand Break Repair: An Ever-Growing Toolbox. Frontiers in molecular biosciences, 7, 24. https://doi.org/10.3389/fmolb.2020.00024
64. Wang, Y., Gan, G., Wang, B., Wu, J., Cao, Y., Zhu, D., Xu, Y., Wang, X., Han, H., Li, X., Ye, M., Zhao, J., & Mi, J. (2017). Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy. EBioMedicine, 17, 45–56. https://doi.org/10.1016/j.ebiom.2017.02.019
65. Ward, I. M., Wu, X., & Chen, J. (2001). Threonine 68 of Chk2 is phosphorylated at sites of DNA strand breaks. The Journal of biological chemistry, 276(51), 47755–47758. https://doi.org/10.1074/jbc.C100587200
66. Xu, B., O'Donnell, A. H., Kim, S. T., & Kastan, M. B. (2002). Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer research, 62(16), 4588–4591.
67. Yeom, C. J., Goto, Y., Zhu, Y., Hiraoka, M., & Harada, H. (2012). Microenvironments and cellular characteristics in the micro tumor cords of malignant solid tumors. International journal of molecular sciences, 13(11), 13949–13965. https://doi.org/10.3390/ijms131113949
68. Yoshida, G. J., & Saya, H. (2016). Therapeutic strategies targeting cancer stem cells. Cancer science, 107(1), 5–11. https://doi.org/10.1111/cas.12817
69. Zhang, H., Luo, H., Jiang, Z., Yue, J., Hou, Q., Xie, R., & Wu, S. (2016). Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma. Journal of radiation research, 57(4), 370–380. https://doi.org/10.1093/jrr/rrw030.
2. Bakkenist, C. J., & Kastan, M. B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature, 421(6922), 499–506. https://doi.org/10.1038/nature01368
3. Balkwill, F., & Mantovani, A. (2001). Inflammation and cancer: back to Virchow?. Lancet (London, England), 357(9255), 539–545. https://doi.org/10.1016/S0140-6736(00)04046-0
4. Bencokova, Z., Kaufmann, M. R., Pires, I. M., Lecane, P. S., Giaccia, A. J., & Hammond, E. M. (2009). ATM activation and signaling under hypoxic conditions. Molecular and cellular biology, 29(2), 526–537. https://doi.org/10.1128/MCB.01301-08
5. Bhatt, A. N., Chauhan, A., Khanna, S., Rai, Y., Singh, S., Soni, R., Kalra, N., & Dwarakanath, B. S. (2015). Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells. BMC cancer, 15, 335. https://doi.org/10.1186/s12885-015-1368-9
6. Brandsma, I., & Gent, D. C. (2012). Pathway choice in DNA double strand break repair: observations of a balancing act. Genome integrity, 3(1), 9. https://doi.org/10.1186/2041-9414-3-9
7. Brown, J. M., Recht, L., & Strober, S. (2017). The Promise of Targeting Macrophages in Cancer Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 23(13), 3241–3250. https://doi.org/10.1158/1078-0432.CCR-16-3122
8. Buscemi, G., Savio, C., Zannini, L., Miccichè, F., Masnada, D., Nakanishi, M., Tauchi, H., Komatsu, K., Mizutani, S., Khanna, K., Chen, P., Concannon, P., Chessa, L., & Delia, D. (2001). Chk2 activation dependence on Nbs1 after DNA damage. Molecular and cellular biology, 21(15), 5214–5222. https://doi.org/10.1128/MCB.21.15.5214-5222.2001
9. Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000). Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes & development, 14(3), 278–288.
10. Chen, Y., Li, Z., Dong, Z., Beebe, J., Yang, K., Fu, L., & Zhang, J. T. (2017). 14-3-3σ Contributes to Radioresistance By Regulating DNA Repair and Cell Cycle via PARP1 and CHK2. Molecular cancer research : MCR, 15(4), 418–428. https://doi.org/10.1158/1541-7786.MCR-16-0366
11. Chevalier, F., Hamdi, D. H., Saintigny, Y., & Lefaix, J. L. (2015). Proteomic overview and perspectives of the radiation-induced bystander effects. Mutation research. Reviews in mutation research, 763, 280–293. https://doi.org/10.1016/j.mrrev.2014.11.008
12. Chu, T. Y., Yang, J. T., Huang, T. H., & Liu, H. W. (2014). Crosstalk with cancer-associated fibroblasts increases the growth and radiation survival of cervical cancer cells. Radiation research, 181(5), 540–547. https://doi.org/10.1667/RR13583.1
13. Chung, F. Y., Huang, M. Y., Yeh, C. S., Chang, H. J., Cheng, T. L., Yen, L. C., Wang, J. Y. & Lin, S. R. (2009). GLUT1 gene is a potential hypoxic marker in colorectal cancer patients. BMC Cancer, 9, 241. https://doi.org/10.1186/1471-2407-9-241
14. Cook, P. J., Thomas, R., Kingsley, P. J., Shimizu, F., Montrose, D. C., Marnett, L. J., Tabar, V. S., Dannenberg, A. J., & Benezra, R. (2016). Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma. Neuro-oncology, 18(10), 1379–1389. https://doi.org/10.1093/neuonc/now049
15. Dasika, G. K., Lin, S. C., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y. (1999). DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene, 18(55), 7883–7899. https://doi.org/10.1038/sj.onc.1203283
16. De Schutter, H., Landuyt, W., Verbeken, E., Goethals, L., Hermans, R., & Nuyts, S. (2005). The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +/- chemotherapy. BMC cancer, 5, 42. https://doi.org/10.1186/1471-2407-5-42
17. Dehne, N., Mora, J., Namgaladze, D., Weigert, A., & Brüne, B. (2017). Cancer cell and macrophage cross-talk in the tumor microenvironment. Current opinion in pharmacology, 35, 12–19. https://doi.org/10.1016/j.coph.2017.04.007
18. Erenpreisa, J., Cragg, M. S. (2001). Mitotic death: a mechanism of survival? A review. Cancer Cell International, 1(1), 1–7. https://doi.org/10.1186/1475-2867-1-1
19. Falcicchio, M., Ward, J. A., Macip, S. & Doveston, R. G. (2020). Regulation of p53 by the 14-3-3 protein interaction network: new opportunities for drug discovery in cancer. Cell Death Discovery, 6, 126. https://doi.org/10.1038/s41420-020-00362-3
20. Falck, J., Petrini, J. H., Williams, B. R., Lukas, J., & Bartek, J. (2002). The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nature genetics, 30(3), 290–294. https://doi.org/10.1038/ng845
21. Fang, J., Zhou, S. H., Fan, J., & Yan, S. X. (2015). Roles of glucose transporter-1 and the phosphatidylinositol 3‑kinase/protein kinase B pathway in cancer radioresistance (review). Molecular medicine reports, 11(3), 1573–1581. https://doi.org/10.3892/mmr.2014.2888
22. Frankenberg-Schwager, M., Gebauer, A., Koppe, C., Wolf, H., Pralle, E., & Frankenberg, D. (2009). Single-strand annealing, conservative homologous recombination, nonhomologous DNA end joining, and the cell cycle-dependent repair of DNA double-strand breaks induced by sparsely or densely ionizing radiation. Radiation research, 171(3), 265–273. https://doi.org/10.1667/RR0784.1
23. Gatei, M., Scott, S. P., Filippovitch, I., Soronika, N., Lavin, M. F., Weber, B., & Khanna, K. K. (2000). Role for ATM in DNA damage-induced phosphorylation of BRCA1. Cancer research, 60(12), 3299–3304.
24. Goffart, N., Lombard, A., Lallemand, F., Kroonen, J., Nassen, J., Di Valentin, E., Berendsen, S., Dedobbeleer, M., Willems, E., Robe, P., Bours, V., Martin, D., Martinive, P., Maquet, P., & Rogister, B. (2017). CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. Neuro-oncology, 19(1), 66–77. https://doi.org/10.1093/neuonc/now136
25. Gorodetska, I., Kozeretska, I., & Dubrovska, A. (2019). BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. Journal of Cancer, 10(9), 2109–2127. https://doi.org/10.7150/jca.30410
26. Harada H. (2011). How can we overcome tumor hypoxia in radiation therapy?. Journal of radiation research, 52(5), 545–556. https://doi.org/10.1269/jrr.11056
27. Harada H. (2016). Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance. Journal of radiation research, 57 Suppl 1(Suppl 1), i99–i105. https://doi.org/10.1093/jrr/rrw012
28. Hashimoto, T., Murata, Y., Urushihara, Y., Shiga, S., Takeda, K., & Hosoi, Y. (2018). Severe hypoxia increases expression of ATM and DNA-PKcs and it increases their activities through Src and AMPK signaling pathways. Biochemical and biophysical research communications, 505(1), 13–19. https://doi.org/10.1016/j.bbrc.2018.09.068
29. Her, J., & Bunting, S. F. (2018). How cells ensure correct repair of DNA double-strand breaks. The Journal of biological chemistry, 293(27), 10502–10511. https://doi.org/10.1074/jbc.TM118.000371
30. Huang, R. X., Zhou, P. K. (2020). DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduction and Targeted Therapy, 5, 60. https://doi.org/10.1038/s41392-020-0150-x
31. Jasin, M., & Rothstein, R. (2013). Repair of strand breaks by homologous recombination. Cold Spring Harbor perspectives in biology, 5(11), a012740. https://doi.org/10.1101/cshperspect.a012740
32. Javle, M., & Curtin, N. J. (2011). The role of PARP in DNA repair and its therapeutic exploitation. British journal of cancer, 105(8), 1114–1122. https://doi.org/10.1038/bjc.2011.382
33. Kastan, M. B., Lim, D. S., Kim, S. T., & Yang, D. (2001). ATM--a key determinant of multiple cellular responses to irradiation. Acta oncologica (Stockholm, Sweden), 40(6), 686–688. https://doi.org/10.1080/02841860152619089
34. Khanna, K. K., Keating, K. E., Kozlov, S., Scott, S., Gatei, M., Hobson, K., Taya, Y., Gabrielli, B., Chan, D., Lees-Miller, S. P., & Lavin, M. F. (1998). ATM associates with and phosphorylates p53: mapping the region of interaction. Nature genetics, 20(4), 398–400. https://doi.org/10.1038/3882
35. Khosravi, R., Maya, R., Gottlieb, T., Oren, M., Shiloh, Y., & Shkedy, D. (1999). Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America, 96(26), 14973–14977. https://doi.org/10.1073/pnas.96.26.14973
36. Krisnawan, V. E., Stanley, J. A., Schwarz, J. K., & DeNardo, D. G. (2020). Tumor Microenvironment as a Regulator of Radiation Therapy: New Insights into Stromal-Mediated Radioresistance. Cancers, 12(10), 2916. https://doi.org/10.3390/cancers12102916
37. Kunkel, M., Moergel, M., Stockinger, M., Jeong, J. H., Fritz, G., Lehr, H. A., & Whiteside, T. L. (2007). Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral oncology, 43(8), 796–803. https://doi.org/10.1016/j.oraloncology.2006.10.009
38. Lee, C. W., & La Thangue, N. B. (1999). Promoter specificity and stability control of the p53-related protein p73. Oncogene, 18(29), 4171–4181. https://doi.org/10.1038/sj.onc.1202793
39. Li, F., Zhou, K., Gao, L., Zhang, B., Li, W., Yan, W., Song, X., Yu, H., Wang, S., Yu, N., & Jiang, Q. (2016). Radiation induces the generation of cancer stem cells: A novel mechanism for cancer radioresistance. Oncology letters, 12(5), 3059–3065. https://doi.org/10.3892/ol.2016.5124
40. Liu, Y-P., Zheng, C-C., Huang, Y-N., Xu, W. W , Li, B. (2021). Molecular mechanisms of chemoand radiotherapy resistance and the potential implications for cancer treatment. MedComm, 2(3), 315–340. https://doi.org/10.1002/mco2.55
41. Mao, Z., Bozzella, M., Seluanov, A., & Gorbunova, V. (2008). Comparison of nonhomologous end joining and homologous recombination in human cells. DNA repair, 7(10), 1765–1771. https://doi.org/10.1016/j.dnarep.2008.06.018
42. Marsden, C. G., Dragon, J. A., Wallace, S. S., & Sweasy, J. B. (2017). Base Excision Repair Variants in Cancer. Methods in enzymology, 591, 119–157. https://doi.org/10.1016/bs.mie.2017.03.003
43. Maya, R., Balass, M., Kim, S. T., Shkedy, D., Leal, J. F., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., Kastan, M. B., Katzir, E., & Oren, M. (2001). ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes & development, 15(9), 1067–1077. https://doi.org/10.1101/gad.886901
44. Meijer, T. W., Kaanders, J. H., Span, P. N., & Bussink, J. (2012). Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clinical cancer research : an official journal of the American Association for Cancer Research, 18(20), 5585–5594. https://doi.org/10.1158/1078-0432.CCR-12-0858
45. Meng, Y., Beckett, M. A., Liang, H., Mauceri, H. J., van Rooijen, N., Cohen, K. S., & Weichselbaum, R. R. (2010). Blockade of tumor necrosis factor alpha signaling in tumor-associated macrophages as a radiosensitizing strategy. Cancer research, 70(4), 1534–1543. https://doi.org/10.1158/0008-5472.CAN-09-2995
46. Mladenov, E., & Iliakis, G. (2011). Induction and repair of DNA double strand breaks: the increasing spectrum of non-homologous end joining pathways. Mutation research, 711(1-2), 61–72. https://doi.org/10.1016/j.mrfmmm.2011.02.005
47. Morgan, M. A., & Lawrence, T. S. (2015). Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways. Clinical cancer research : an official journal of the American Association for Cancer Research, 21(13), 2898–2904. https://doi.org/10.1158/1078-0432.CCR-13-3229
48. Moureau, S., Luessing, J., Harte, E. C., Voisin, M., & Lowndes, N. F. (2016). A role for the p53
49. tumour suppressor in regulating the balance between homologous recombination and non-homologous end joining. Open biology, 6(9), 160225. https://doi.org/10.1098/rsob.160225
50. Nakashima, R., Goto, Y., Koyasu, S., Kobayashi, M., Morinibu, A., Yoshimura, M., Hiraoka, M., Hammond, E. M., & Harada, H. (2017). UCHL1-HIF-1 axis-mediated antioxidant property of cancer cells as a therapeutic target for radiosensitization. Scientific reports, 7(1), 6879. https://doi.org/10.1038/s41598-017-06605-1
51. O'Connell, M. J., Walworth, N. C., & Carr, A. M. (2000). The G2-phase DNA-damage checkpoint. Trends in cell biology, 10(7), 296–303. https://doi.org/10.1016/s0962-8924(00)01773-6
52. Olcina, M. M., Grand, R. J., & Hammond, E. M. (2014). ATM activation in hypoxia – causes and consequences. Molecular & cellular oncology, 1(1), e29903. https://doi.org/10.4161/mco.29903
53. Patra, K. C., & Hay, N. (2014). The pentose phosphate pathway and cancer. Trends in biochemical sciences, 39(8), 347–354. https://doi.org/10.1016/j.tibs.2014.06.005
54. Sharma, A., Singh, K., & Almasan, A. (2012). Histone H2AX phosphorylation: a marker for DNA damage. Methods in molecular biology (Clifton, N.J.), 920, 613–626. https://doi.org/10.1007/978-1-61779-998-3_40
55. Shu, K. X., Li, B., & Wu, L. X. (2007). The p53 network: p53 and its downstream genes. Colloids and surfaces. B, Biointerfaces, 55(1), 10–18. https://doi.org/10.1016/j.colsurfb.2006.11.003 Sia, J., Szmyd, R., Hau, E., & Gee, H. E. (2020). Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer. Frontiers in cell and developmental biology, 8, 41. https://doi.org/10.3389/fcell.2020.00041
56. Suwa, T., Kobayashi, M., Nam, J. M., Harada H. (2021). Tumor microenvironment and radioresistance. Experimental & molecular medicine, 53, 1029–1035. https://doi.org/10.1038/s12276-021-00640-9
57. Suzuki, K., Mori, I., Nakayama, Y., Miyakoda, M., Kodama, S., & Watanabe, M. (2001). Radiation-induced senescence-like growth arrest requires TP53 function but not telomere shortening. Radiation research, 155(1 Pt 2), 248–253. https://doi.org/10.1667/0033-7587(2001)155 [0248:rislga]2.0.co;2
58. Suzuki, K., Yokoyama, S., Waseda, S., Kodama, S., & Watanabe, M. (2003). Delayed reactivation of p53 in the progeny of cells surviving ionizing radiation. Cancer research, 63(5), 936–941.
59. Tang, L., Wei, F., Wu, Y., He, Y., Shi, L., Xiong, F., Gong, Z., Guo, C., Li, X., Deng, H., Cao, K., Zhou, M., Xiang, B., Li, X., Li, Y., Li, G., Xiong, W., & Zeng, Z. (2018). Role of metabolism in cancer cell radioresistance and radiosensitization methods. Journal of experimental & clinical cancer research : CR, 37(1), 87. https://doi.org/10.1186/s13046-018-0758-7
60. Tang, Y., He, Y., Shi, L., Yang, L., Wang, J., Lian, Y., Fan, C., Zhang, P., Guo, C., Zhang, S., Gong, Z., Li, X., Xiong, F., Li, X., Li, Y., Li, G., Xiong, W., & Zeng, Z. (2017). Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma. Oncotarget, 8(24), 39001–39011. https://doi.org/10.18632/oncotarget.16545
61. Telarovic, I., Wenger, R. H. & Pruschy, M. (2021). Interfering with Tumor Hypoxia for Radiotherapy Optimization. Journal of experimental & clinical cancer research : CR, 40 (1), 197. https://doi.org/10.1186/s13046-021-02000-x
62. Velegzhaninov, I. O., Belykh, E. S., Rasova, E. E., Pylina, Y. I., Shadrin, D. M., & Klokov, D. Y. (2020). Radioresistance, DNA Damage and DNA Repair in Cells With Moderate Overexpression of RPA1. Frontiers in genetics, 11, 855. https://doi.org/10.3389/fgene.2020.00855
63. Vítor, A. C., Huertas, P., Legube, G., & de Almeida, S. F. (2020). Studying DNA Double-Strand Break Repair: An Ever-Growing Toolbox. Frontiers in molecular biosciences, 7, 24. https://doi.org/10.3389/fmolb.2020.00024
64. Wang, Y., Gan, G., Wang, B., Wu, J., Cao, Y., Zhu, D., Xu, Y., Wang, X., Han, H., Li, X., Ye, M., Zhao, J., & Mi, J. (2017). Cancer-associated Fibroblasts Promote Irradiated Cancer Cell Recovery Through Autophagy. EBioMedicine, 17, 45–56. https://doi.org/10.1016/j.ebiom.2017.02.019
65. Ward, I. M., Wu, X., & Chen, J. (2001). Threonine 68 of Chk2 is phosphorylated at sites of DNA strand breaks. The Journal of biological chemistry, 276(51), 47755–47758. https://doi.org/10.1074/jbc.C100587200
66. Xu, B., O'Donnell, A. H., Kim, S. T., & Kastan, M. B. (2002). Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer research, 62(16), 4588–4591.
67. Yeom, C. J., Goto, Y., Zhu, Y., Hiraoka, M., & Harada, H. (2012). Microenvironments and cellular characteristics in the micro tumor cords of malignant solid tumors. International journal of molecular sciences, 13(11), 13949–13965. https://doi.org/10.3390/ijms131113949
68. Yoshida, G. J., & Saya, H. (2016). Therapeutic strategies targeting cancer stem cells. Cancer science, 107(1), 5–11. https://doi.org/10.1111/cas.12817
69. Zhang, H., Luo, H., Jiang, Z., Yue, J., Hou, Q., Xie, R., & Wu, S. (2016). Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma. Journal of radiation research, 57(4), 370–380. https://doi.org/10.1093/jrr/rrw030.
Abstract views: 161 PDF Downloads: 125
Published
2022-01-17
How to Cite
Chorna, I. (2022). MOLECULAR MECHANISMS UNDERLYING CANCER CELL RADIORESISTANCE. Scientific Journal of Polonia University, 48(5), 142-151. https://doi.org/10.23856/4818
Section
HEALTH, ENVIRONMENT, DEVELOPMENT
