Targeting YWHAG protein: A unified therapeutic strategy against tumors or neurodegenerative diseases
Download PDF Share Subscribe
logo
All Journals Login

Ageing and Cancer Research & Treatment
  1. Home
  2. Articles
  3. Article

Targeting YWHAG protein: A unified therapeutic strategy against tumors or neurodegenerative diseases

Rui Jing
1
,
Tongxin Jia
1
,
Xiang Pan
2
,
Zhenying Lu
1
,
Runzi Zheng
1
,
Jiahua Liu
1
,
Shuting Jia
1
,
Jing Liu
1,*
*Correspondence to: Jing Liu, Laboratory of Molecular Genetics of Aging and Tumor, Medical School，Kunming University of Science and Technology, Kunming 650500, Yunnan, China. E-mail: jingling@kust.edu.cn
Ageing Cancer Res Treat. 2026;3:202607. 10.70401/acrt.2026.0028
Received: March 05, 2026Accepted: June 26, 2026Published: June 29, 2026
Tips Icon
This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

YWHAG is a subtype of the 14-3-3 protein family that regulates the transduction of multiple signaling pathways in cells, such as the PI3K-AKT and MAPK pathways, by recognizing and binding to specific phosphorylated target protein motifs. These signaling pathways are widely found to be abnormally activated or shut down in human diseases, such as cancer and neurodegenerative diseases. Different evidence has shown that the expression levels and functions of YWHAG in different tumors are not the same. Meanwhile, the potential functions of YWHAG in these diseases and its role in regulating abnormal signaling pathways are still unknown. Therefore, further exploration and research are needed to determine YWHAG’s core role in regulating signaling pathways and whether YWHAG can be a therapeutic target for diseases to develop corresponding drugs. This review will revisit the structure and function of YWHAG, elaborate on the newly identified YWHAG-interacting proteins in recent years, summarize the functions of YWHAG in cancer while comparing it with the homologous family member YWHAZ, explore the functions of YWHAG in neurodegenerative diseases, and present our perspectives on drug-screening strategies targeting YWHAG.

Keywords

14-3-3 protein，YWHAG, tumors, neurodegenerative, duality, targeted strategies

References

  • 1. Sheikh AH, Zacharia I, Tabassum N, Hirt H, Ntoukakis V. 14-3-3 proteins as a major hub for plant immunity. Trends Plant Sci. 2024;29(11):1245-1253.
    [DOI]
  • 2. Inamdar SM, Lankford CK, Laird JG, Novbatova G, Tatro N, Whitmore SS, et al. Analysis of 14-3-3 isoforms expressed in photoreceptors. Exp Eye Res. 2018;170:108-116.
    [DOI] [PubMed] [PMC]
  • 3. Gogl G, Tugaeva KV, Eberling P, Kostmann C, Trave G, Sluchanko NN. Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms. Nat Commun. 2021 Mar 15;12(1):1677.
    [DOI] [PubMed] [PMC]
  • 4. Darling DL, Yingling J, Wynshaw‐Boris A. Role of 14-3-3 proteins in eukaryotic signaling and development. Curr Top Dev Biol. 2005;68:281-315.
    [DOI]
  • 5. Hwang Y, An HT, Kang M, Ko J. Roles of 14-3-3β and γ in regulation of the glucocorticoid receptor transcriptional activation and hepatic gluconeogenesis. Biochem Biophys Res Commun. 2018;501(3):800-806.
    [DOI]
  • 6. Aitken A. 14-3-3 proteins: A historic overview. Semin Cancer Biol. 2006;16(3):162-172.
    [DOI]
  • 7. Gogl G, Tugaeva KV, Eberling P, Kostmann C, Trave G, Sluchanko NN. Hierarchized phosphotarget binding by the seven human 14-3-3 isoforms. Nat Commun. 2021;12(1):1677.
    [DOI] [PubMed] [PMC]
  • 8. Martin H, Rostas J, Patel Y, Aitken A. Subcellular localisation of 14-3-3 isoforms in rat brain using specific antibodies. J Neurochem. 1994;63(6):2259-2265.
    [DOI] [PubMed]
  • 9. Guo Y, Chen SD, You J, Huang SY, Chen YL, Zhang Y, et al. Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer’s disease. Nat Hum Behav. 2024;8(10):2047-2066.
    [DOI]
  • 10. Peng Y, Zhu L, Bai Q, Wang L, Li Q. Serum level of YWHAG as a diagnostic marker of cognitive impairment in Parkinson’s disease patients. Acta Neurol Belg. 2024;124(3):879-885.
    [DOI] [PubMed] [PMC]
  • 11. Pair FS, Yacoubian TA. 14-3-3 proteins: Novel pharmacological targets in neurodegenerative diseases. Trends Pharmacol Sci. 2021;42(4):226-238.
    [DOI]
  • 12. Ni J, Wang J, Fu Y, Yan C, Zhu M, Jiang Y, et al. Functional genetic variants in centrosome-related genes CEP72 and YWHAG confer susceptibility to gastric cancer. Arch Toxicol. 2020;94(8):2861-2872.
    [DOI] [PubMed]
  • 13. Jin T, Yin T, Xu R, Liu H, Yuan S, Xue Y, et al. Exploring the role of disulfidptosis-related signatures in immune microenvironment, prognosis and therapeutic strategies of cervical cancer. Transl Oncol. 2024;44:101938.
    [DOI] [PubMed] [PMC]
  • 14. Jiang W, Luo H, Shen Z, Zhang W, Chen A, Zhu X. Down-regulation and gene hypermethylation of the 14-3-3 gamma in uterine leiomyoma. Front Biosci. 2016;21(6):1286-1295.
    [DOI] [PubMed]
  • 15. Xiao B, Smerdon SJ, Jones DH, Dodson GG, Soneji Y, Aitken A, et al. Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. Nature. 1995;376(6536):188-191.
    [DOI] [PubMed]
  • 16. Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, et al. The structural basis for 14-3-3: Phosphopeptide binding specificity. Cell. 1997;91(7):961-971.
    [DOI]
  • 17. Tzivion G, Shen YH, Zhu J. 14-3-3 proteins; bringing new definitions to scaffolding. Oncogene. 2001;20(44):6331-6338.
    [DOI]
  • 18. Psenakova K, Petrvalska O, Kylarova S, Lentini Santo D, Kalabova D, Herman P, et al. 14-3-3 protein directly interacts with the kinase domain of calcium/calmodulin-dependent protein kinase kinase (CaMKK2). Biochim Biophys Acta Gen Subj. 2018;1862(7):1612-1625.
    [DOI] [PubMed]
  • 19. Park E, Rawson S, Li K, Kim BW, Ficarro SB, Pino GG, et al. Architecture of autoinhibited and active BRAF-MEK1-14-3-3 complexes. Nature. 2019;575(7783):545-550.
    [DOI] [PubMed] [PMC]
  • 20. Muslin AJ, Xing H. 14-3-3 proteins: Regulation of subcellular localization by molecular interference. Cell Signal. 2000;12(11-12):703-709.
    [DOI] [PubMed]
  • 21. Xu Y, Ren J, He X, Chen H, Wei T, Feng W. YWHA/14-3-3 proteins recognize phosphorylated TFEB by a noncanonical mode for controlling TFEB cytoplasmic localization. Autophagy. 2019;15(6):1017-1030.
    [DOI] [PubMed] [PMC]
  • 22. Morrison DK. The 14-3-3 proteins: Integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol. 2009;19(1):16-23.
    [DOI] [PubMed] [PMC]
  • 23. Dumitru CA, Bankfalvi A, Gu X, Eberhardt WE, Zeidler R, Lang S, et al. Neutrophils activate tumoral CORTACTIN to enhance progression of orohypopharynx carcinoma. Front Immunol. 2013;4:33.
    [DOI] [PubMed] [PMC]
  • 24. Ammer AG, Weed SA. Cortactin branches out: Roles in regulating protrusive actin dynamics. Cell Motil Cytoskeleton. 2008;65(9):687-707.
    [DOI] [PubMed] [PMC]
  • 25. Wang Y, Cao Y, Chen Y, Cheng H, Liu Z, Wang M, et al. YWHAG promotes colorectal cancer progression by regulating the CTTN-Wnt/β-catenin signaling axis. Med Oncol. 2024;41(5):100.
    [DOI] [PubMed] [PMC]
  • 26. Grisendi S, Mecucci C, Falini B, Pandolfi PP. Nucleophosmin and cancer. Nat Rev Cancer. 2006;6(7):493-505.
    [DOI]
  • 27. Bose A, Modi K, Dey S, Dalvi S, Nadkarni P, Sudarshan M, et al. 14–3-3γ prevents centrosome duplication by inhibiting NPM1 function. Genes Cells. 2021;26(6):426-446.
    [DOI]
  • 28. Chen D, Zou J, Zhao Z, Tang X, Deng Z, Jia J, et al. TXNDC9 promotes hepatocellular carcinoma progression by positive regulation of MYC-mediated transcriptional network. Cell Death Dis. 2018;9(11):1110.
    [DOI] [PubMed] [PMC]
  • 29. Lu J, Holmgren A. The thioredoxin antioxidant system. Free Radic Biol Med. 2014;66:75-87.
    [DOI]
  • 30. Wang J, Pan X, Li J, Zhao J. TXNDC9 knockdown inhibits lung adenocarcinoma progression by targeting YWHAG. Mol Med Rep. 2022;25(6):203.
    [DOI] [PubMed] [PMC]
  • 31. Wang W, Li J, Zhou Q. The biological function of cytoplasm-translocated ENDOG (endonuclease G). Autophagy. 2024;20(2):445-447.
    [DOI] [PubMed] [PMC]
  • 32. Sheng N, Yan L, Wu K, You W, Gong J, Hu L, et al. TRIP13 promotes tumor growth and is associated with poor prognosis in colorectal cancer. Cell Death Dis. 2018;9(3):402.
    [DOI] [PubMed] [PMC]
  • 33. Du G, Yu X, Chen Y, Cai W. miR-1-3p suppresses colorectal cancer cell proliferation and metastasis by inhibiting YWHAZ-mediated epithelial-mesenchymal transition. Front Oncol. 2021;11:634596.
    [DOI] [PubMed] [PMC]
  • 34. Tang Y, Liu S, Li N, Guo W, Shi J, Yu H, et al. 14-3-3ζ promotes hepatocellular carcinoma venous metastasis by modulating hypoxia-inducible factor-1α. Oncotarget. 2016;7(13):15854-15867.
    [DOI] [PubMed] [PMC]
  • 35. Dong N, Gu WW, Yang L, Lian WB, Jiang J, Zhu HJ, et al. miR-3074-5p suppresses non-small cell lung cancer progression by targeting the YWHAZ/Hsp27 axis. Int Immunopharmacol. 2024;138:112547.
    [DOI] [PubMed]
  • 36. Zhao GY, Ding JY, Lu CL, Lin ZW, Guo J. The overexpression of 14-3-3ζ and Hsp27 promotes non–small cell lung cancer progression. Cancer. 2014;120(5):652-663.
    [DOI] [PubMed]
  • 37. Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, et al. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med. 2010;16(2):214-218.
    [DOI] [PubMed] [PMC]
  • 38. Chu YW, Wang CR, Weng FB, Yan ZJ, Wang C. microRNA-222 contributed to cell proliferation, invasion and migration via regulating YWHAG in osteosarcoma. Eur Rev Med Pharmacol Sci. 2018;22(9):2588-2597.
    [DOI] [PubMed]
  • 39. Zheng Y, Miao Y, Xie J, Lin Y, Yao Q, Cai J, et al. Long noncoding RNA lysophospholipase-like 1-2 as ceRNA modulates glioma metastasis by regulating miR-217/YWHAG. Am J Transl Res. 2020;12(8):4204-4215.
    [PubMed] [PMC]
  • 40. Shen Q, Hu X, Zhou L, Zou S, Sun LZ, Zhu X. Overexpression of the 14-3-3γ protein in uterine leiomyoma cells results in growth retardation and increased apoptosis. Cell Signal. 2018;45:43-53.
    [DOI] [PubMed]
  • 41. Xu J, Wang J, He Z, Chen P, Jiang X, Chen Y, et al. LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer. Cell Death Dis. 2021;12(7):648.
    [DOI] [PubMed] [PMC]
  • 42. Tian T, He S, Hao H, Guan B, Gong Y, Fan J, et al. YWHAG promotes bladder cancer metastasis by regulating TMOD3 to activate ERK1/2 and JNK phosphorylation in the MAPK pathway. J Transl Med. 2024;22(1):1159.
    [DOI] [PubMed] [PMC]
  • 43. Hiraoka E, Mimae T, Ito M, Kadoya T, Miyata Y, Ito A, et al. Breast cancer cell motility is promoted by 14-3-3γ. Breast Cancer. 2019;26(5):581-593.
    [DOI]
  • 44. Liu K, Han H, Huang S, Song L, Jiang J, Zheng D. YWHAG mediated epithelial-mesenchymal transition facilitates tumor progression and metastatic spread in non-small cell lung cancer. Cell Signal. 2025;136:112139.
    [DOI] [PubMed]
  • 45. Zheng H, Tang Y, Zang H, Luo J, Zhou H, Zou Y, et al. YWHAG promotes the progression of lung adenocarcinoma through the JAK2/STAT3 pathway. Cancer Cell Int. 2025;25(1):112.
    [DOI] [PubMed] [PMC]
  • 46. Huang R, Kong Y, Luo Z, Li Q. LncRNA NDUFA6-DT: A comprehensive analysis of a potential LncRNA biomarker and its regulatory mechanisms in gliomas. Genes. 2024;15(4):483.
    [DOI] [PubMed] [PMC]
  • 47. Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556-W560.
    [DOI] [PubMed] [PMC]
  • 48. Berg D, Holzmann C, Riess O. 14-3-3 proteins in the nervous system. Nat Rev Neurosci. 2003;4(9):752-762.
    [DOI]
  • 49. Boston PF, Jackson P, Thompson RJ. Human 14-3-3 protein: Radioimmunoassay, tissue distribution, and cerebrospinal fluid levels in patients with neurological disorders. J Neurochem. 1982;38(5):1475-1482.
    [DOI] [PubMed]
  • 50. Bennison SA, Blazejewski SM, Liu X, Hacohen-Kleiman G, Sragovich S, Zoidou S, et al. The cytoplasmic localization of ADNP through 14-3-3 promotes sex-dependent neuronal morphogenesis, cortical connectivity, and calcium signaling. Mol Psychiatry. 2023;28(5):1946-1959.
    [DOI] [PubMed] [PMC]
  • 51. Khan S, Barve KH, Kumar MS. Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer’s disease. CN. 2020;18(11):1106-1125.
    [DOI]
  • 52. Twarowski B, Herbet M. Inflammatory processes in Alzheimer’s disease: Pathomechanism, diagnosis and treatment: A review. Int J Mol Sci. 2023;24(7):6518.
    [DOI]
  • 53. Sathe G, Na CH, Renuse S, Madugundu AK, Albert M, Moghekar A, et al. Quantitative proteomic profiling of cerebrospinal fluid to identify candidate biomarkers for Alzheimer’s disease. Proteomics Clinical Apps. 2019;13(4):1800105.
    [DOI]
  • 54. Do AN, Ali M, Timsina J, Wang L, Western D, Liu M, et al. CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer’s disease. MedRxiv [Preprint]. 2024.
    [DOI]
  • 55. Park H, Lee YB, Chang KA. miR-200c suppression increases tau hyperphosphorylation by targeting 14-3-3γ in early stage of 5xFAD mouse model of Alzheimer’s disease. Int J Biol Sci. 2022;18(5):2220-2234.
    [DOI] [PubMed] [PMC]
  • 56. Hayes MT. Parkinson’s disease and Parkinsonism. Am J Med. 2019;132(7):802-807.
    [DOI]
  • 57. Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, et al. Alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 1999;19(14):5782-5791.
    [DOI] [PubMed] [PMC]
  • 58. Berg D, Holzmann C, Riess O. 14-3-3 proteins in the nervous system. Nat Rev Neurosci. 2003;4(9):752-762.
    [DOI]
  • 59. Kawamoto Y, Akiguchi I, Nakamura S, Honjyo Y, Shibasaki H, Budka H. 14-3-3 proteins in lewy bodies in Parkinson disease and diffuse lewy body disease brains. J Neuropathol Exp Neurol. 2002;61(3):245-253.
    [DOI]
  • 60. McFerrin MB, Chi X, Cutter G, Yacoubian TA. Dysregulation of 14-3-3 proteins in neurodegenerative diseases with Lewy body or Alzheimer pathology. Ann Clin Transl Neurol. 2017;4(7):466-477.
    [DOI]
  • 61. Nichols RJ, Dzamko N, Morrice NA, Campbell DG, Deak M, Ordureau A, et al. 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson’s disease-associated mutations and regulates cytoplasmic localization. Biochem J. 2010;430(3):393-404.
    [DOI] [PubMed] [PMC]
  • 62. Martinez Fiesco JA, Beilina A, Alvarez de la Cruz A, Li N, Metcalfe RD, Cookson MR, et al. 14-3-3 binding maintains the Parkinson’s associated kinase LRRK2 in an inactive state. Nat Commun. 2025;16:7226.
    [DOI]
  • 63. George G, Valiya Parambath S, Lokappa SB, Varkey J. Construction of Parkinson’s disease marker-based weighted protein-protein interaction network for prioritization of co-expressed genes. Gene. 2019;697:67-77.
    [DOI] [PubMed]
  • 64. Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT. Natural products in drug discovery: Advances and opportunities. Nat Rev Drug Discov. 2021;20(3):200-216.
    [DOI] [PubMed] [PMC]
  • 65. Li J, Sun Y, Li G, Cheng C, Sui X, Wu Q. The extraction, determination, and bioactivity of curcumenol: A comprehensive review. Molecules. 2024;29(3):656.
    [DOI] [PubMed] [PMC]
  • 66. Mao Z, Zhong L, Zhuang X, Liu H, Peng Y. Curcumenol targeting YWHAG inhibits the pentose phosphate pathway and enhances antitumor effects of cisplatin. Evid Based Complement Alternat Med. 2022;2022:3988916.
    [DOI] [PubMed] [PMC]
  • 67. Oyabambi AO, Areola ED, Olatunji LA, Soladoye AO. Uric acid is a key player in salt-induced endothelial dysfunction: The therapeutic role of Stigma maydis (corn silk) extract. Appl Physiol Nutr Metab. 2020;45(1):67-71.
    [DOI] [PubMed]
  • 68. Zhang H, Jiang H, Zhao M, Xu Y, Liang J, Ye Y, et al. Treatment of gout with TCM using turmeric and corn silk: A concise review article and pharmacology network analysis. Evid Based Complementary Altern Med. 2022;2022:3143733.
    [DOI]
  • 69. Diener C, Keller A, Meese E. Emerging concepts of miRNA therapeutics: From cells to clinic. Trends Genet. 2022;38(6):613-626.
    [DOI]
  • 70. Huang W. microRNAs: biomarkers, diagnostics, and therapeutics. In: Huang J, Borchert GM, Dou D, Huan J, Lan W, Tan M, Wu B, editors. Bioinformatics in microRNA research. New York: Springer; 2017. p. 57-67.
    [DOI]
  • 71. Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today. 1992;13(4):136-142.
    [DOI]
  • 72. Konstantinidou M, Zingiridis M, Pennings MAM, Fragkiadakis M, Virta JM, Revalde JL, et al. Scaffold-hopping for molecular glues targeting the 14-3-3/ERα complex. Nat Commun. 2025;16:6467.
    [DOI]
  • 73. De Vries-van Leeuwen IJ, da Costa Pereira D, Flach KD, Piersma SR, Haase C, Bier D, et al. Interaction of 14-3-3 proteins with the estrogen receptor alpha F domain provides a drug target interface. Proc Natl Acad Sci U S A. 2013;110(22):8894-8899.
    [DOI] [PubMed] [PMC]
  • 74. Katz LS, Visser EJ, Plitzko KF, Pennings MAM, Cossar PJ, Tse IL, et al. Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity. Nat Commun. 2025;16(1):2110.
    [DOI] [PubMed] [PMC]
  • 75. Liu Y, Bai J, Li D, Cang Y. Routes to molecular glue degrader discovery. Trends Biochem Sci. 2025;50(2):134-142.
    [DOI]
  • 76. Larasati YA, Solis GP, Koval A, Korff C, Katanaev VL. A personalized 14-3-3 disease-targeting workflow yields repositioning drug candidates. Cells. 2025;14(8):559.
    [DOI] [PubMed] [PMC]
  • 77. Kay DF, Raza HG, Doveston RG, Leney AC. Hydrogen-deuterium exchange mass spectrometry for molecular glue characterization. Adv Sci. 2025;12(41):e08543.
    [DOI] [PubMed] [PMC]
  • 78. Lee JXT, Tan WR, Low ZS, Lee JQ, Chua D, Yeo WDC, et al. YWHAG deficiency disrupts the EMT-associated network to induce oxidative cell death and prevent metastasis. Adv Sci. 2023;10(31):e2301714.
    [DOI] [PubMed] [PMC]
  • 79. Raungrut P, Wongkotsila A, Champoochana N, Lirdprapamongkol K, Svasti J, Thongsuksai P. Knockdown of 14-3-3γ suppresses epithelial–mesenchymal transition and reduces metastatic potential of human non-small cell lung cancer cells. Anticancer Res. 2018;38(6):3507-3514.
    [DOI]
  • 80. Vilmont V, Nowakowski RS, Zhou Y. Role of the YWHAG gene mutations in developmental and epileptic encephalopathy. Front Neurosci. 2025;19:1641250.
    [DOI] [PubMed] [PMC]
  • 81. Cho E, Park J, Hwang EM, Kim HW, Park JY. 14-3-3γ haploinsufficiency leads to altered dopamine pathway and Parkinson’s disease-like motor incoordination in mice. Mol Brain. 2023;16(1):2.
    [DOI] [PubMed] [PMC]
  • 82. Oh HS, Urey DY, Karlsson L, Zhu Z, Shen Y, Farinas A, et al. A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer’s disease. Nat Med. 2025;31(5):1592-1603.
    [DOI] [PubMed] [PMC]
  • 83. Li ZK, Liao JL, Luo MR, Fang SJ, Huang WZ, Zhang DY. Neuro-tumor interactions: Multi-dimensional mechanisms of neurotransmitter regulation in tumor immune evasion and metabolic reprogramming. World J Clin Oncol. 2025;16(10):108954.
    [DOI] [PubMed] [PMC]
  • 84. Wang X, Fan Y, Wang Q, Shu X, Lin J, Guo J, et al. Tumor-infiltrating nerves: Unraveling the role of cancer neuroscience in tumorigenesis, disease progression, and emerging therapies. Discov Oncol. 2025;16(1):1209.
    [DOI] [PubMed] [PMC]
  • 85. Wang X, Yan Y, Li L, Li T, Thakur A, Zhang K, et al. The influence of neuro-tumor interactions on tumorigenesis and therapeutic response. Exp Hematol Oncol. 2026;15(1):18.
    [DOI] [PubMed] [PMC]
  • 86. Fraser KB, Moehle MS, Daher JPL, Webber PJ, Williams JY, Stewart CA, et al. LRRK2 secretion in exosomes is regulated by 14-3-3. Hum Mol Genet. 2013;22(24):4988-5000.
    [DOI]
  • 87. Schapansky J, Nardozzi JD, LaVoie MJ. The complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson’s disease. Neuroscience. 2015;302:74-88.
    [DOI] [PubMed] [PMC]
  • 88. Ma Y, Li C, Huang Y, Wang Y, Xia X, Zheng JC. Exosomes released from neural progenitor cells and induced neural progenitor cells regulate neurogenesis through miR-21a. Cell Commun Signal. 2019;17(1):96.
    [DOI] [PubMed] [PMC]
  • 89. Winkler F, Venkatesh HS, Amit M, Batchelor T, Demir IE, Deneen B, et al. Cancer neuroscience: State of the field, emerging directions. Cell. 2023;186(8):1689-1707.
    [DOI]
  • 90. Mancusi R, Monje M. The neuroscience of cancer. Nature. 2023;618(7965):467-479.
    [DOI]
  • 91. Hanahan D, Monje M. Cancer hallmarks intersect with neuroscience in the tumor microenvironment. Cancer Cell. 2023;41(3):573-580.
    [DOI] [PubMed] [PMC]
  • 92. Yaniv D, Mattson B, Talbot S, Gleber-Netto FO, Amit M. Targeting the peripheral neural-tumour microenvironment for cancer therapy. Nat Rev Drug Discov. 2024;23(10):780-796.
    [DOI] [PubMed] [PMC]
  • 93. Martinez Fiesco JA, Beilina A, Alvarez de la Cruz A, Li N, Metcalfe RD, Cookson MR, et al. 14-3-3 binding maintains the Parkinson’s associated kinase LRRK2 in an inactive state. Nat Commun. 2025;16:7226.
    [DOI]
  • 94. Konstantinidou M, Zingiridis M, Pennings MA, Fragkiadakis M, Virta JM, Revalde JL, et al. Scaffold-hopping for molecular glues targeting the 14-3-3/ERα complex. Nat Commun.2025;16:6467.
    [DOI]
  • 95. Stevers LM, Wolter M, Carlile GW, MacDonald D, Richard L, Gielkens F, et al. Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR. Nat Commun. 2022;13:3586.
    [DOI]
  • 96. Meng EC, Goddard TD, Pettersen EF, Couch GS, Pearson ZJ, Morris JH, et al. UCSF ChimeraX: Tools for structure building and analysis. Protein Sci. 2023;32(11):e4792.
    [DOI] [PubMed] [PMC]
  • 97. Bai Q, Yu J, Li Y, Ma J, Gou Y. MicroRNA-182 promoted esophageal squamous cell carcinoma cell growth and metastasis via targeting YWHAG. J BUON. 2018;23(5):1439-1447.
    [PubMed]
  • 98. Chen G, Zhang Z, Li Y, Wang L, Liu Y. LncRNA PTPRG-AS1 promotes the metastasis of hepatocellular carcinoma by enhancing YWHAG. J Oncol. 2021;2021:3624306.
    [DOI] [PubMed] [PMC]
  • 99. Wang P, Deng Y, Fu X. miR-509-5p suppresses the proliferation, migration, and invasion of non-small cell lung cancer by targeting YWHAG. Biochem Biophys Res Commun. 2017;482(4):935-941.
    [DOI] [PubMed]
  • 100. Yoo JO, Kwak SY, An HJ, Bae IH, Park MJ, Han YH. miR-181b-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization by directly targeting YWHAG. Biochim Biophys Acta. 2016;1863(7 Pt A):1601-1611.
    [DOI] [PubMed]
  • 101. Park H, Lee YB, Chang KA. miR-200c suppression increases tau hyperphosphorylation by targeting 14-3-3γ in early stage of 5xFAD mouse model of Alzheimer’s disease. Int J Biol Sci. 2022;18(5):2220-2234.
    [DOI] [PubMed] [PMC]
  • 102. Zhou X, Wang Z, Xu B, Ji N, Meng P, Gu L, et al. Long non-coding RNA NORAD protects against cerebral ischemia/reperfusion injury induced brain damage, cell apoptosis, oxidative stress and inflammation by regulating miR-30a-5p/YWHAG. Bioengineered. 2021;12(2):9174-9188.
    [DOI] [PubMed] [PMC]
  • 103. Perdigão-Henriques R, Petrocca F, Altschuler G, Thomas MP, Le MT, Tan SM, et al. miR-200 promotes the mesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes. Oncogene. 2016;35(2):158-172.
    [DOI] [PubMed]

© The Author(s) 2026. This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Publisher’s Note

Science Exploration remains a neutral stance on jurisdictional claims in published maps and institutional affiliations. The views expressed in this article are solely those of the author(s) and do not reflect the opinions of the Editors or the publisher.

Share And Cite

×

Science Exploration Style
Jing R, Jia T, Pan X, Lu Z, Zheng R, Liu J, et al. Targeting YWHAG protein: A unified therapeutic strategy against tumors or neurodegenerative diseases. Ageing Cancer Res Treat. 2026;3:202607. https://doi.org/10.70401/acrt.2026.0028

Submit a Manuscript
Author Instructions
Cite this Article
Export Citation
Article Metrics
0
View
0
Download
Cited
Article Updates
Related Articles
Citation Icon Get citation

Ageing and Cancer Research & Treatment

pISSN 2972-4759
eISSN 2972-4767
acrtjournal@sciexplor.com

Navigation

About the Journal
Editorial Process
Author Instructions
Editorial Board
Editorial Policies
Contact Us

Follow us