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image of Unravelling the Association between FOXO3a and Cancer Cell Senescence: An Insight into its Role and Biological Pathway

Abstract

This review explores the intricate relationship between FOXO3a and cellular senescence in cancer, highlighting its complex and context-dependent function. FOXO3a, a transcription factor commonly known as a tumor suppressor, exhibits paradoxical roles in cancer biology. This review describes FOXO3a's dual functions in promoting tumor suppression and progression, its interplay with senescence pathways, and its impact on cancer cell phenotypes. Senescence is also known to be a tumor suppressor and a barrier against malignancies. However, persistent senescence has been found to create an adverse effect due to cancer progression and therapeutic endeavors. The review also discusses the potential of senescence management and FOXO3a modulation as novel therapeutic strategies in cancer treatment. Recent advancements in proteomics research, including FOXO3a's interactions with microRNAs, post-translational modifications, and protein-protein interactions, are also elaborated. This paper concludes by emphasizing the need to understand the role of FOXO3a in cancer biology and its potential as a biomarker and therapeutic target.

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2025-09-29
2025-12-18
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References

  1. Cancer Indonesia 2020 country profile. 2020 https://www.who.int/publications/m/item/cancer-idn-2020
    [Google Scholar]
  2. Hanahan D. Hallmarks of cancer: New dimensions. Cancer Discov. 2022 12 1 31 46 10.1158/2159‑8290.CD‑21‑1059 35022204
    [Google Scholar]
  3. Calcinotto A. Kohli J. Zagato E. Pellegrini L. Demaria M. Alimonti A. Cellular senescence: Aging, cancer, and injury. Physiol. Rev. 2019 99 2 1047 1078 10.1152/physrev.00020.2018 30648461
    [Google Scholar]
  4. Mylonas A. O’Loghlen A. Cellular senescence and ageing: Mechanisms and interventions. Frontiers in Aging 2022 3 866718 10.3389/fragi.2022.866718 35821824
    [Google Scholar]
  5. Yaswen P. Campisi J. Oncogene-induced senescence pathways weave an intricate tapestry. Cell 2007 128 2 233 234 10.1016/j.cell.2007.01.005 17254959
    [Google Scholar]
  6. Yaeger R. Mezzadra R. Sinopoli J. Molecular characterization of acquired resistance to krasg12c–egfr inhibition in colorectal cancer. Cancer Discov. 2023 13 1 41 55 10.1158/2159‑8290.CD‑22‑0405 36355783
    [Google Scholar]
  7. Yang J. Liu M. Hong D. Zeng M. Zhang X. The paradoxical role of cellular senescence in cancer. Front. Cell Dev. Biol. 2021 9 722205 10.3389/fcell.2021.722205 34458273
    [Google Scholar]
  8. Wang M. Morsbach F. Sander D. EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks. Cancer Res. 2011 71 19 6261 6269 10.1158/0008‑5472.CAN‑11‑0213 21852385
    [Google Scholar]
  9. Mirzayans R. Scott A. Cameron M. Murray D. Induction of accelerated senescence by γ radiation in human solid tumor-derived cell lines expressing wild-type TP53. Radiat. Res. 2005 163 1 53 62 10.1667/RR3280 15606307
    [Google Scholar]
  10. Lee J.Y. Reyes N. Woo S.H. Senescent fibroblasts in the tumor stroma rewire lung cancer metabolism and plasticity. bioRxiv 2024 2024.07.29 605645. 10.1101/2024.07.29.605645 39131266
    [Google Scholar]
  11. Ohtani N. The roles and mechanisms of senescence-associated secretory phenotype (SASP): Can it be controlled by senolysis? Inflamm. Regen. 2022 42 1 11 10.1186/s41232‑022‑00197‑8 35365245
    [Google Scholar]
  12. Ou H.L. Hoffmann R. González-López C. Doherty G.J. Korkola J.E. Muñoz-Espín D. Cellular senescence in cancer: From mechanisms to detection. Mol. Oncol. 2021 15 10 2634 2671 10.1002/1878‑0261.12807 32981205
    [Google Scholar]
  13. Alimirah F. Pulido T. Valdovinos A. Cellular senescence promotes skin carcinogenesis through p38MAPK and p44/42 MAPK signaling. Cancer Res. 2020 80 17 3606 3619 10.1158/0008‑5472.CAN‑20‑0108 32641409
    [Google Scholar]
  14. Freund A. Patil C.K. Campisi J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J. 2011 30 8 1536 1548 10.1038/emboj.2011.69 21399611
    [Google Scholar]
  15. Prašnikar E. Borišek J. Perdih A. Senescent cells as promising targets to tackle age-related diseases. Ageing Res. Rev. 2021 66 101251 10.1016/j.arr.2020.101251 33385543
    [Google Scholar]
  16. Sagiv A. NKG2D ligands mediate immunosurveillance of senescent cells. Aging 2016 8 2 328 344 10.18632/aging.100897 26878797
    [Google Scholar]
  17. Kale A. Role of immune cells in the removal of deleterious senescent cells. Immun. Ageing 2020 17 16 10.1186/s12979‑020‑00187‑9
    [Google Scholar]
  18. Ruscetti M. Leibold J. Bott M.J. NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination. Science 2018 362 6421 1416 1422 10.1126/science.aas9090 30573629
    [Google Scholar]
  19. Marin I. Boix O. Garcia-Garijo A. Cellular senescence is immunogenic and promotes antitumor immunity. Cancer Discov. 2023 13 2 410 431 10.1158/2159‑8290.CD‑22‑0523 36302218
    [Google Scholar]
  20. Reynolds L.E. Maallin S. Haston S. Martinez-Barbera J.P. Hodivala-Dilke K.M. Pedrosa A.R. Effects of senescence on the tumour microenvironment and response to therapy. FEBS J. 2024 291 11 2306 2319 10.1111/febs.16984 37873605
    [Google Scholar]
  21. Wang L. Lankhorst L. Bernards R. Exploiting senescence for the treatment of cancer. Nat. Rev. Cancer 2022 22 6 340 355 10.1038/s41568‑022‑00450‑9 35241831
    [Google Scholar]
  22. Salminen A. Kaarniranta K. Kauppinen A. Immunosenescence: The potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency. Cell. Mol. Life Sci. 2019 76 10 1901 1918 10.1007/s00018‑019‑03048‑x 30788516
    [Google Scholar]
  23. Fisher DT Appenheimer MM Evans SS The two faces of IL-6 in the tumor microenvironment. United States: Academic Press 2014 26 1 38 47 10.1016/j.smim.2014.01.008
    [Google Scholar]
  24. Ortiz-Montero P. Londoño-Vallejo A. Vernot J.P. Senescence associated IL-6 and IL-8 cytokines induce a self- and cross reinforced senescence/inflammatory milieu strengthening tumorigenic capabilities in the MCF-7 breast cancer cell line. Cell Commun. Signal. 2017 15 1 17 10.1186/s12964‑017‑0172‑3 28472950
    [Google Scholar]
  25. Liu H. Wang S. Xin J. Wang J. Yao C. Zhang Z. Role of NKG2D and its ligands in cancer immunotherapy. 2019 Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6834480/
    [Google Scholar]
  26. Laberge R.M. Awad P. Campisi J. Desprez P.Y. Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron. 2012 5 1 39 44 10.1007/s12307‑011‑0069‑4 21706180
    [Google Scholar]
  27. Zingoni A. Cecere F. Vulpis E. Genotoxic stress induces senescence-associated adam10-dependent release of nkg2d mic ligands in multiple myeloma cells. J. Immunol. 2015 195 2 736 748 10.4049/jimmunol.1402643 26071561
    [Google Scholar]
  28. Chakrabarty A. Chakraborty S. Bhattacharya R. Chowdhury G. Senescence-induced chemoresistance in triple negative breast cancer and evolution-based treatment strategies. Front. Oncol. 2021 11 674354 10.3389/fonc.2021.674354 34249714
    [Google Scholar]
  29. Karabicici M. Alptekin S. Fırtına Karagonlar Z. Erdal E. Doxorubicin‐induced senescence promotes stemness and tumorigenicity in EpCAM−/CD133− nonstem cell population in hepatocellular carcinoma cell line, HuH‐7. Mol. Oncol. 2021 15 8 2185 2202 10.1002/1878‑0261.12916 33524223
    [Google Scholar]
  30. Fasano C. Disciglio V. Bertora S. Signorile M.L. Simone C. FOXO3a from the nucleus to the mitochondria: A round trip in cellular stress response. Cells 2019 8 9 1110 10.3390/cells8091110 31546924
    [Google Scholar]
  31. Liu Y. Wang Y. Li X. Jia Y. Wang J. Ao X. FOXO3a in cancer drug resistance. Cancer Lett. 2022 540 215724 10.1016/j.canlet.2022.215724 35545128
    [Google Scholar]
  32. Das T.P. Suman S. Alatassi H. Ankem M.K. Damodaran C. Inhibition of AKT promotes FOXO3a-dependent apoptosis in prostate cancer. Cell Death Dis. 2016 7 2 2111 10.1038/cddis.2015.403 26913603
    [Google Scholar]
  33. Li J. Ma W. Cheng X. Activation of FOXO3 pathway is involved in polyphyllin I-induced apoptosis and cell cycle arrest in human bladder cancer cells. Arch. Biochem. Biophys. 2020 687 108363 10.1016/j.abb.2020.108363 32335049
    [Google Scholar]
  34. Yan J. Yang S. Tian H. Zhang Y. Zhao H. RETRACTED ARTICLE: Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer. Cell Death Dis. 2020 11 11 943 10.1038/s41419‑020‑03154‑w 33139695
    [Google Scholar]
  35. Mei W. Role and regulation of FOXO3a: New insights into breast cancer therapy. Front. Pharmacol. 2024 15 1346745 10.3389/fphar.2024.1346745 38505423
    [Google Scholar]
  36. Qian K. Wang G. Cao R. Capsaicin suppresses cell proliferation, induces cell cycle arrest and ROS production in bladder cancer cells through FOXO3a-mediated pathways. Molecules 2016 21 10 1406 10.3390/molecules21101406 27775662
    [Google Scholar]
  37. Ock C.W. Kim G.D. Harmine hydrochloride mediates the induction of G2/M cell cycle arrest in breast cancer cells by regulating the MAPKs and AKT/FOXO3a signaling pathways. Molecules 2021 26 21 6714 10.3390/molecules26216714 34771123
    [Google Scholar]
  38. Nestal de Moraes G. Bella L. Zona S. Burton M.J. Lam E.W-F. Insights into a critical role of the foxo3a-foxm1 axis in dna damage response and genotoxic drug resistance. Curr. Drug Targets 2016 17 2 164 177 10.2174/1389450115666141122211549 25418858
    [Google Scholar]
  39. Qian Z. Ren L. Wu D. Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis. Int. J. Cancer 2017 140 12 2792 2804 10.1002/ijc.30690 28295288
    [Google Scholar]
  40. Wanandi S.I. Hardiany N.S. Siregar N.C. Sadikin M. Suppression of manganese superoxide dismutase activity in rotenone-treated human glioblastoma T98G cells reduces cell viability. Asian J. Pharm. Clin. Res. 2018 11 1 48 10.22159/ajpcr.2018.v11i1.19777
    [Google Scholar]
  41. Cao G. The rules and regulatory mechanisms of FOXO3 on inflammation, metabolism, cell death and aging in hosts. Life Sci. 2023 328 121877 10.1016/j.lfs.2023.121877 37352918
    [Google Scholar]
  42. Hui R.C.Y. Francis R.E. Guest S.K. Doxorubicin activates FOXO3a to induce the expression of multidrug resistance gene ABCB1 (MDR1) in K562 leukemic cells. Mol. Cancer Ther. 2008 7 3 670 678 10.1158/1535‑7163.MCT‑07‑0397 18347152
    [Google Scholar]
  43. Xu K. Zhang Z. Pei H. Wang H. Li L. Xia Q. FoxO3a induces temozolomide resistance in glioblastoma cells via the regulation of β-catenin nuclear accumulation. Oncol. Rep. 2017 37 4 2391 2397 10.3892/or.2017.5459 28260024
    [Google Scholar]
  44. Marlow LA von Roemeling CA Cooper SJ Foxo3a drives proliferation in anaplastic thyroid carcinoma via transcriptional regulation of cyclin A1: A paradigm shift that impacts current therapeutic strategies. J Cell Sci 2012 125 Pt 18 10.1242/jcs.097428 22718346 : jcs.097428.
    [Google Scholar]
  45. Storz P. Döppler H. Copland J.A. Simpson K.J. Toker A. FOXO3a promotes tumor cell invasion through the induction of matrix metalloproteinases. Mol. Cell. Biol. 2009 29 18 4906 4917 10.1128/MCB.00077‑09 19564415
    [Google Scholar]
  46. Yu S. FOXO3a promotes gastric cancer cell migration and invasion through the induction of cathepsin L. Oncotarget 2016 7 23 34773 34784 10.18632/oncotarget.8977 27127880
    [Google Scholar]
  47. Rehman A. Kim Y. Kim H. FOXO3a expression is associated with lymph node metastasis and poor disease-free survival in triple-negative breast cancer. J. Clin. Pathol. 2018 71 9 806 813 10.1136/jclinpath‑2018‑205052 29588373
    [Google Scholar]
  48. Yang F. Liu W. Chen H. Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression. J. Zhejiang Univ. Sci. B 2020 21 1 64 76 10.1631/jzus.B1900551 31898443
    [Google Scholar]
  49. Santo E.E. Stroeken P. Sluis P.V. Koster J. Versteeg R. Westerhout E.M. FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma. Cancer Res. 2013 73 7 2189 2198 10.1158/0008‑5472.CAN‑12‑3767 23378341
    [Google Scholar]
  50. Kim G.D. Induction of hepatocellular carcinoma cell cycle arrest and apoptosis by Dendropanax morbifera leveille leaf extract via the PI3K/AKT/mTOR pathway. J. Cancer Prev. 2023 28 4 185 193 10.15430/JCP.2023.28.4.185 38205361
    [Google Scholar]
  51. Wang Y. Zhou Y. Graves D.T. FOXO transcription factors: Their clinical significance and regulation. Biomed Res. Int. 2014 2014 925350 10.1155/2014/925350 24864265
    [Google Scholar]
  52. Li C. Hu W.L. Lu M.X. Xiao G.F. Resveratrol induces apoptosis of benign prostatic hyperplasia epithelial cell line (BPH-1) through p38 MAPK-FOXO3a pathway. BMC Complement. Altern. Med. 2019 19 1 233 10.1186/s12906‑019‑2648‑8 31464618
    [Google Scholar]
  53. Shrestha A. Nepal S. Kim M.J. Critical role of AMPK/FoxO3A axis in globular adiponectin‐induced cell cycle arrest and apoptosis in cancer cells. J. Cell. Physiol. 2016 231 2 357 369 10.1002/jcp.25080 26089158
    [Google Scholar]
  54. Consolaro F. Ghaem-Maghami S. Bortolozzi R. FOXO3a and posttranslational modifications mediate glucocorticoid sensitivity in B-ALL. Mol. Cancer Res. 2015 13 12 1578 1590 10.1158/1541‑7786.MCR‑15‑0127 26376801
    [Google Scholar]
  55. Hu Q. Wang G. Peng J. Knockdown of SIRT1 suppresses bladder cancer cell proliferation and migration and induces cell cycle arrest and antioxidant response through FOXO3A-mediated pathways. BioMed Res. Int. 2017 2017 1 14 10.1155/2017/3781904 29147649
    [Google Scholar]
  56. Hardiany N.S. Remifta Putra M.A. Penantian R.M. Antarianto R.D. Effects of fasting on FOXO3 expression as an anti-aging biomarker in the liver. Heliyon 2023 9 2 13144 10.1016/j.heliyon.2023.e13144 36718153
    [Google Scholar]
  57. Tsai W.B. Chung Y.M. Takahashi Y. Xu Z. Hu M.C.T. Functional interaction between FOXO3a and ATM regulates DNA damage response. Nat. Cell Biol. 2008 10 4 460 467 10.1038/ncb1709 18344987
    [Google Scholar]
  58. Adamowicz M. Vermezovic J. d’Adda di Fagagna F. NOTCH1 inhibits activation of atm by impairing the formation of an ATM-FOXO3a-KAT5/Tip60 complex. Cell Rep. 2016 16 8 2068 2076 10.1016/j.celrep.2016.07.038 27524627
    [Google Scholar]
  59. Rupp M. Hagenbuchner J. Rass B. FOXO3-mediated chemo protection in high-stage neuroblastoma depends on wild-type TP53 and SESN3. Oncogene 2017 36 44 6190 6203 10.1038/onc.2017.288 28869600
    [Google Scholar]
  60. Chung Y.M. Park S.H. Tsai W.B. FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. Nat. Commun. 2012 3 1 1000 10.1038/ncomms2008 22893124
    [Google Scholar]
  61. Laphanuwat P Likasitwatanakul P Sittithumcharee G Cyclin d1 depletion interferes with cancer oxidative balance and sensitizes cancer cells to senescence. J Cell Sci 2018 131 12 : jcs.214726. 10.1242/jcs.214726 29880532
    [Google Scholar]
  62. Grasso D. Garcia M.N. Hamidi T. Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating KrasG12D-induced senescence. Cell Death Differ. 2014 21 10 1633 1641 10.1038/cdd.2014.74 24902898
    [Google Scholar]
  63. Ji S. Zheng Z. Liu S. Resveratrol promotes oxidative stress to drive DLC1 mediated cellular senescence in cancer cells. Exp. Cell Res. 2018 370 2 292 302 10.1016/j.yexcr.2018.06.031 29964052
    [Google Scholar]
  64. Park S.Y. Bae Y.S. Inactivation of the FoxO3a transcription factor is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated senescence in human colon cancer and breast cancer cells. Biochem. Biophys. Res. Commun. 2016 478 1 18 24 10.1016/j.bbrc.2016.07.106 27470586
    [Google Scholar]
  65. Zhang J.W. Zhang D. Yu B.P. Senescent cells in cancer therapy: Why and how to remove them. Cancer Lett. 2021 520 68 79 10.1016/j.canlet.2021.07.002 34237406
    [Google Scholar]
  66. Wang S. Sun Y. Yao L. Xing Y. Yang H. Ma Q. The Role of microRNA-23a-3p in the Progression of Human Aging Process by Targeting FOXO3a. Mol. Biotechnol. 2024 66 2 277 287 10.1007/s12033‑023‑00746‑7 37087718
    [Google Scholar]
  67. Dianxiu Wang Wei Geng Lu Han Pro-carcinogenic actions of miR-155/FOXO3a in colorectal cancer development. Cell. Mol. Biol. 2023 69 10 160 165 10.14715/cmb/2023.69.10.23 37953568
    [Google Scholar]
  68. Sun L. Liu J. Bao D. Hu C. Zhao Y. Chen S. Progress in the study of FOXO3a interacting with microRNA to regulate tumourigenesis development. Front. Oncol. 2023 13 1293968 10.3389/fonc.2023.1293968 37965449
    [Google Scholar]
  69. Wang B. Li Y. Wang H. FOXO3a is stabilized by USP18-mediated de-ISGylation and inhibits TGF-β1-induced fibronectin expression. J. Investig. Med. 2020 68 3 786 791 10.1136/jim‑2019‑001145 31874933
    [Google Scholar]
  70. Mathivanan S. Chunchagatta Lakshman P.K. Singh M. Structure of a 14-3-3ε:FOXO3a pS253 phosphopeptide complex reveals 14-3-3 isoform-specific binding of forkhead box class o transcription factor (FOXO) phosphoproteins. ACS Omega 2022 7 28 24344 24352 10.1021/acsomega.2c01700 35874228
    [Google Scholar]
  71. Wang C. Tu X. Jiang Y. Prognostic value of high FOXO3a expression in patients with solid tumors: A meta-analysis and systematic review. Int. J. Biol. Markers 2022 37 2 210 217 10.1177/03936155221095879 35484793
    [Google Scholar]
  72. Fondevila F. Association of FOXO3 expression with tumor pathogenesis, prognosis and clinicopathological features in hepatocellular carcinoma: A systematic review with meta-analysis. Cancers 2021 13 21 5349 10.3390/cancers13215349 34771514
    [Google Scholar]
  73. Song S.S. Ying J.F. Zhang Y.N. High expression of FOXO3 is associated with poor prognosis in patients with hepatocellular carcinoma. Oncol. Lett. 2020 19 4 3181 3188 10.3892/ol.2020.11430 32256814
    [Google Scholar]
  74. Ricci E. Fava M. Rizza P. Foxo3a inhibits tamoxifen-resistant breast cancer progression by inducing integrin α5 expression. Cancers 2022 14 1 214 10.3390/cancers14010214 35008379
    [Google Scholar]
  75. Liu H. Song Y. Qiu H. Downregulation of FOXO3a by DNMT1 promotes breast cancer stem cell properties and tumorigenesis. Cell Death Differ. 2020 27 3 966 983 10.1038/s41418‑019‑0389‑3 31296961
    [Google Scholar]
  76. Cao Y. Li P. Wang H. Li L. Li Q. SIRT3 promotion reduces resistance to cisplatin in lung cancer by modulating the FOXO3/CDT1 axis. Cancer Med. 2021 10 4 1394 1404 10.1002/cam4.3728 33655712
    [Google Scholar]
  77. Tang Z. Zhang Y. Yu Z. Luo Z. Metformin suppresses stemness of non-small-cell lung cancer induced by paclitaxel through FOXO3a. Int. J. Mol. Sci. 2023 24 23 16611 10.3390/ijms242316611 38068934
    [Google Scholar]
  78. Feng S Jiang Z-J Yu D Li J Liu G Sun J-J FOXO3a expression and its diagnostic value in pancreatic ductal adenocarcinoma. 2018 11 11 5422 5429 Available from: https://pubmed.ncbi.nlm.nih.gov/31949625/
    [Google Scholar]
  79. Kumazoe M. Takai M. Bae J. FOXO3 is essential for CD44 expression in pancreatic cancer cells. Oncogene 2017 36 19 2643 2654 10.1038/onc.2016.426 27893718
    [Google Scholar]
  80. Ding D. Ao X. Li M. FOXO3a‐dependent Parkin regulates the development of gastric cancer by targeting ATP‐binding cassette transporter E1. J. Cell. Physiol. 2021 236 4 2740 2755 10.1002/jcp.30040 32914432
    [Google Scholar]
  81. Ni D. Ma X. Li H.Z. Downregulation of FOXO3a promotes tumor metastasis and is associated with metastasis-free survival of patients with clear cell renal cell carcinoma. Clin. Cancer Res. 2014 20 7 1779 1790 10.1158/1078‑0432.CCR‑13‑1687 24486593
    [Google Scholar]
  82. Li P. Chen T. Kuang P. Aurora-A/FOXO3A/SKP2 axis promotes tumor progression in clear cell renal cell carcinoma and dual-targeting Aurora-A/SKP2 shows synthetic lethality. Cell Death Dis. 2022 13 7 606 10.1038/s41419‑022‑04973‑9 35831273
    [Google Scholar]
  83. Qian C. Liu Q. FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β-catenin signaling pathway. Mol. Med. Rep. 2021 24 5 796 10.3892/mmr.2021.12436 34515328
    [Google Scholar]
  84. Liang C. Dong Z. Cai X. Hypoxia induces sorafenib resistance mediated by autophagy via activating FOXO3a in hepatocellular carcinoma. Cell Death Dis. 2020 11 11 1017 10.1038/s41419‑020‑03233‑y 33250518
    [Google Scholar]
  85. Ahn H. Kim H. Abdul R. Overexpression of forkhead box O3a and its association with aggressive phenotypes and poor prognosis in human hepatocellular carcinoma. Am. J. Clin. Pathol. 2018 149 2 117 127 10.1093/ajcp/aqx132 29365018
    [Google Scholar]
  86. Imada K. Shiota M. Kuroiwa K. FOXO3a expression regulated by ERK signaling is inversely correlated with Y‐box binding protein‐1 expression in prostate cancer. Prostate 2017 77 2 145 153 10.1002/pros.23254 27699813
    [Google Scholar]
  87. Tao Y. Liu S. Lu J. FOXO3a-ROS pathway is involved in androgen-induced proliferation of prostate cancer cell. BMC Urol. 2022 22 1 70 10.1186/s12894‑022‑01020‑9 35488328
    [Google Scholar]
  88. Gao Z. Li Z. Liu Y. Liu Z. Forkhead box O3 promotes colon cancer proliferation and drug resistance by activating MDR1 expression. Mol. Genet. Genomic Med. 2019 7 3 554 10.1002/mgg3.554 30623608
    [Google Scholar]
  89. Yu Y. Peng K. Li H. SP1 upregulated FoxO3a promotes tumor progression in colorectal cancer. Oncol. Rep. 2018 39 5 2235 2242 10.3892/or.2018.6323 29565456
    [Google Scholar]
  90. Dong Z. Yang J. Li L. FOXO3a-SIRT6 axis suppresses aerobic glycolysis in melanoma. Int. J. Oncol. 2020 56 3 728 742 10.3892/ijo.2020.4964 32124950
    [Google Scholar]
  91. Yan F. Liao R. Lin S. Deng X. Little P. Zheng W. Forkhead box protein O3 suppresses uveal melanoma development by increasing the expression of Bcl-2-like protein 11 and cyclin-dependent kinase inhibitor 1B. Mol. Med. Rep. 2017 17 2 3109 3114 10.3892/mmr.2017.8215 29257235
    [Google Scholar]
  92. Qin Y. Sun W. Wang Z. RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma. Cell Death Dis. 2022 13 3 270 10.1038/s41419‑022‑04728‑6 35338124
    [Google Scholar]
  93. Phuagkhaopong S. Janpattanapichai J. Sirirak N. Khemawoot P. Vivithanaporn P. Suknuntha K. Transcriptome analysis reveals a role of FOXO3 in antileukemia/lymphoma properties of panduratin A. Sci. Rep. 2024 14 1 24795 10.1038/s41598‑024‑75630‑8 39433897
    [Google Scholar]
  94. Osswald C.D. Xie L. Guan H. Fine-tuning of FOXO3A in cHL as a survival mechanism and a hallmark of abortive plasma cell differentiation. Blood 2018 131 14 1556 1567 Available from: http://www.ncbi.nlm.nih.gov/geo/
    [Google Scholar]
  95. Shou Z. Lin L. Liang J. Li J.L. Chen H.Y. Expression and prognosis of FOXO3a and HIF-1α in nasopharyngeal carcinoma. J. Cancer Res. Clin. Oncol. 2012 138 4 585 593 10.1007/s00432‑011‑1125‑7 22209974
    [Google Scholar]
  96. Luo M. Wu C. Guo E. FOXO3a knockdown promotes radioresistance in nasopharyngeal carcinoma by inducing epithelial-mesenchymal transition and the Wnt/β-catenin signaling pathway. Cancer Lett. 2019 455 26 35 10.1016/j.canlet.2019.04.019 31022422
    [Google Scholar]
  97. Kang Y. He P. Wang H. Brazilin induces FOXO3A dependent autophagic cell death by disturbing calcium homeostasis in osteosarcoma cells. Cancer Chemother. Pharmacol. 2018 82 3 479 491 10.1007/s00280‑018‑3633‑5 29987368
    [Google Scholar]
  98. Park S.H. Lee J. Kang M.A. Jang K. Kim J. Mitoxantrone induces apoptosis in osteosarcoma cells through regulation of the Akt/FOXO3 pathway. Oncol. Lett. 2018 15 6 9687 9696 10.3892/ol.2018.8547 29928344
    [Google Scholar]
  99. He C. Lu S. Wang X. FOXO3a protects glioma cells against temozolomide-induced DNA double strand breaks via promotion of BNIP3-mediated mitophagy. Acta Pharmacol. Sin. 2021 42 8 1324 1337 10.1038/s41401‑021‑00663‑y 33879840
    [Google Scholar]
  100. Sun D. Yang S. Zhang X. Forkhead box protein O3a promotes glioma cell resistance to temozolomide by regulating matrix metallopeptidase and β-catenin. Oncol. Lett. 2021 21 4 328 10.3892/ol.2021.12580 33692860
    [Google Scholar]
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  • Article Type:
    Review Article
Keywords: senescence ; malignancies ; FOXO3a ; resistance ; cell cycle arrest ; Cancer
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