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TFF3 sensitizes cervical carcinoma cells to cisplatin toxicity by binding to IGF2R

Cancer Gene Therapy volume 33, pages 155–168 (2026)Cite this article

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Abstract

Cisplatin resistance causes ineffectiveness of cisplatin-based treatment for cervical carcinoma. The combination of cisplatin and other chemotherapeutic drugs is an available strategy to overcome this problem. However, chemotherapeutic drugs combined with cisplatin may show tissue toxicity and systemic side effects. Thus, there is a great need of seeking effective substitutes for these chemotherapeutic drugs to improve combination therapy. Here, we found that inactivating IL-6/JAK2/STAT3 signaling pathway sensitized carcinoma cells to cisplatin toxicity by increasing cisplatin accumulation, impairing DNA damage repair, and inhibiting the initiation and development of autophagy, which subsequently caused the increases in DNA damage levels and apoptosis rates in cisplatin-treated cells. We predicted that TFF3 negatively regulated transduction in the IL-6/JAK2/STAT3 pathway based on in silico analysis of the differentially expressed genes (DEGs) between highly trefoil factor 3(TFF3)-encoding mRNA-expressing carcinoma tissues and low-expressing counterparts, and experimentally determined that both ectopic expression of TFF3-encoding gene and TFF3 administration inhibited IL-6-induced STAT3 activation in carcinoma cells. Mechanistically, upon binding to IGF2R, TFF3 stabilized IGF2R by inhibiting the ubiquitin-proteasome degradation pathway to inactivate Akt and thereby STAT3. Moreover, we discovered that TFF3 administration antagonized protective effects of IL-6 stimulation against tumor-killing capacity of cisplatin. Based on these findings, we consider that TFF3 may be employed as a cisplatin sensitizer and have advantages over traditional chemotherapeutic drugs in cisplatin-based combination therapy, since it is a naturally occurring protein in cervical tissue.

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Fig. 1: IL-6 prevents cisplatin-induced double-strand breaks in DNAs.
Fig. 2: TFF3 inhibits the IL-6-induced activation of the JAK2/STAT3 signaling pathway.
Fig. 3: IGF2R mediates the TFF3’s inhibitory effect on the activation of the JAK2/STAT3 signaling pathway.
Fig. 4: TFF3 stabilizes the IGF2R protein to inactivate Akt protein.
Fig. 5: TFF3 overcomes IL-6-induced cisplatin resistance by inactivating Akt.

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Data availability

All relevant data generated in this study are available within the article and supplementary files. The original data can be requested from the corresponding author for reasonable purposes. The bioinformatics analysis data were obtained from the TCGA (https://www.cancer.gov/) and GEO (https://www.ncbi.nlm.nih.gov/geo/).

Code availability

The “limma” package was employed to determine the differentially expressed genes. The “clusterProfiler” and “enrichplot” packages were used to perform gene enrichement analysis. The expression levels of TFF3 and XRCC4-encoding mRNAs were obtained from GSE7410, GSE39001 and GSE3514. And the “GEOquery” and “ggplot2” packages were separately exploited to group data and to conduct boxplot analysis that provides insightful visualization.

References

  1. Vu M, Yu J, Awolude OA, Chuang L. Cervical cancer worldwide. Curr Probl Cancer. 2018;42:457–65.

    PubMed  Google Scholar 

  2. Brooke G, Wendel S, Banerjee A, Wallace N. Opportunities to advance cervical cancer prevention and care. Tumour Virus Res. 2024;18:200292.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Włoszek E, Krupa K, Skrok E, Budzik MP, Deptała A, Badowska-Kozakiewicz A. HPV and cervical cancer-biology, prevention, and treatment updates. Curr Oncology 2025;32:122.

  4. Ghosh S. Cisplatin: the first metal based anticancer drug. Bioorg Chem. 2019;88:102925.

    CAS  PubMed  Google Scholar 

  5. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharm. 2014;740:364–78.

    CAS  Google Scholar 

  6. Achkar IW, Abdulrahman N, Al-Sulaiti H, Joseph JM, Uddin S, Mraiche F. Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway. J Transl Med. 2018;16:96.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Trimmer EE, Essigmann JM. Cisplatin. Essays Biochem. 1999;34:191–211.

    CAS  PubMed  Google Scholar 

  8. Lorusso D, Petrelli F, Coinu A, Raspagliesi F, Barni S. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol. 2014;133:117–23.

    CAS  PubMed  Google Scholar 

  9. Rottenberg S, Disler C, Perego P. The rediscovery of platinum-based cancer therapy. Nat Rev Cancer. 2021;21:37–50.

    CAS  PubMed  Google Scholar 

  10. Zhang J, Ye Z, Tew KD, Townsend DM. Cisplatin chemotherapy and renal function. Adv Cancer Res. 2021;152:305–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang X, Zhou Y, Wang D, Wang Y, Zhou Z, Ma X, et al. Cisplatin-induced ototoxicity: from signaling network to therapeutic targets. Biomed Pharmacother Biomed Pharmacother. 2023;157:114045.

    CAS  PubMed  Google Scholar 

  12. Zhu H, Luo H, Zhang W, Shen Z, Hu X, Zhu X. Molecular mechanisms of cisplatin resistance in cervical cancer. Drug Des, Dev Ther. 2016;10:1885–95.

    CAS  Google Scholar 

  13. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, et al. Molecular mechanisms of cisplatin resistance. Oncogene. 2012;31:1869–83.

    CAS  PubMed  Google Scholar 

  14. Thim L, May FEB. Structure of mammalian trefoil factors and functional insights. Cellular Mol Life Sci CMLS. 2005;62:2956–73.

    CAS  Google Scholar 

  15. Wong WM, Poulsom R, Wright NA. Trefoil peptides. Gut. 1999;44:890–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kjellev S. The trefoil factor family - small peptides with multiple functionalities. Cellular Mol Life Sci CMLS. 2009;66:1350–69.

    CAS  PubMed  Google Scholar 

  17. Belovari T, Bijelić N, Tolušić Levak M, Baus Lončar M. Trefoil factor family peptides TFF1 and TFF3 in the nervous tissues of developing mouse embryo. Bosn J Basic Med Sci. 2015;15:33–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Braga Emidio N, Hoffmann W, Brierley SM, Muttenthaler M. Trefoil factor family: unresolved questions and clinical perspectives. Trends Biochem Sci. 2019;44:387–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Muskett FW, May FEB, Westley BR, Feeney J. Solution structure of the disulfide-linked dimer of human intestinal trefoil factor (TFF3): the intermolecular orientation and interactions are markedly different from those of other dimeric trefoil proteins. Biochemistry. 2003;42:15139–47.

    CAS  PubMed  Google Scholar 

  20. Yang Y, Lin Z, Lin Q, Bei W, Guo J. Pathological and therapeutic roles of bioactive peptide trefoil factor 3 in diverse diseases: recent progress and perspective. Cell Death Dis. 2022;13:62.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Buda A, Jepson MA, Pignatelli M. Regulatory function of trefoil peptides (TFF) on intestinal cell junctional complexes. Cell Commun Adhes. 2012;19:63–68.

    CAS  PubMed  Google Scholar 

  22. Aamann L, Vestergaard EM, Grønbæk H. Trefoil factors in inflammatory bowel disease. World J Gastroenterol. 2014;20:3223–30.

    PubMed  PubMed Central  Google Scholar 

  23. Cui H, Wang S, Song F, Cheng X, Nan G, Zhao Y, et al. CD147 receptor is essential for TFF3-mediated signaling, regulating colorectal cancer progression. Signal Transduct Target Ther. 2021;6:268.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Yang L, Zhang X, Zhang J, Liu Y, Ji T, Mou J, et al. Low expression of TFF3 in papillary thyroid carcinoma may correlate with poor prognosis but high immune cell infiltration. Future Oncol. 2022;18:333–48.

    CAS  PubMed  Google Scholar 

  25. Belle NM, Ji Y, Herbine K, Wei Y, Park J, Zullo K, et al. TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths. Nat Commun. 2019;10:4408.

    PubMed  PubMed Central  Google Scholar 

  26. Yang T, Fu X, Tian R, Cui H, Li L, Han J, et al. TFF3 promotes clonogenic survival of colorectal cancer cells through upregulation of EP4 via activation of STAT3. Transl Cancer Res. 2023;12:1503–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. You M, Chen Y, Chong Q, Wu M, Pandey V, Chen R, et al. Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular. Oncotarget. 2017;8:39323–44.

    PubMed  PubMed Central  Google Scholar 

  28. Große-Kreul J, Busch M, Winter C, Pikos S, Stephan H, Dünker N. Forced trefoil factor family peptide 3 (TFF3) expression reduces growth, viability, and tumorigenicity of human retinoblastoma cell lines. PLoS ONE. 2016;11:e0163025.

    PubMed  PubMed Central  Google Scholar 

  29. You M, Chen Y, Chong Q, Wu M, Pandey V, Chen R, et al. Trefoil factor 3 mediation of oncogenicity and chemoresistance in hepatocellular carcinoma is AKT-BCL-2 dependent. Oncotarget. 2017;8:39323–44.

    PubMed  PubMed Central  Google Scholar 

  30. Takano T, Yamada H. Trefoil factor 3 (TFF3): a promising indicator for diagnosing thyroid follicular carcinoma. Endocr J. 2009;56:9–16.

    CAS  PubMed  Google Scholar 

  31. Maděrka M, Dvořák V, Hambálek J, Stejskal D, Krejčí ŠM, Langová K, et al. Serum concentrations of S100-A11 and AIF-1 are elevated in cervical cancer patients with lymph node involvement. Ceska Gynekol. 2021;86:17–21.

    PubMed  Google Scholar 

  32. Houben T, Harder S, Schlüter H, Kalbacher H, Hoffmann W. Different forms of TFF3 in the human saliva: heterodimerization with IgG fc binding protein (FCGBP). Int J Mol Sci. 2019;20:5000.

  33. Karimi-Zarchi M, Abbasi H, Javaheri A, Hadadan A, Meibodi B, Tabatabaei RS, et al. Association of IL-12b rs3212227 and IL-6 rs1800795 polymorphisms with susceptibility to cervical cancer: a systematic review and meta-analysis. Asian Pac J Cancer Prev APJCP. 2020;21:1197–206.

    CAS  PubMed  Google Scholar 

  34. Cai C, Peng X, Zhang Y. Serum IL-6 level predicts the prognosis and diagnosis in cervical cancer patients. Int J Womens Health. 2022;14:655–63.

    PubMed  PubMed Central  Google Scholar 

  35. Konishi H, Okamoto K, Ohmori Y, Yoshino H, Ohmori H, Ashihara M, et al. An orally available, small-molecule interferon inhibits viral replication. Sci Rep. 2012;2:259.

    PubMed  PubMed Central  Google Scholar 

  36. Ghandadi M, Sahebkar A. Interleukin-6: a critical cytokine in cancer multidrug resistance. Curr Pharm Des. 2016;22:518–26.

    CAS  PubMed  Google Scholar 

  37. Galluzzi L, Vitale I, Michels J, Brenner C, Szabadkai G, Harel-Bellan A, et al. Systems biology of cisplatin resistance: past, present, and future. Cell Death Dis. 2014;5:e1257.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Jiang M, Jia K, Wang L, Li W, Chen B, Liu Y, et al. Alterations of DNA damage response pathway: biomarker and therapeutic strategy for cancer immunotherapy. Acta Pharm Sin B. 2021;11:2983–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol. 2017;18:495–506.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang Y, Guo R, Wang S, Jiang X, Cui H, Guo Y, et al. Autophagy-related proteins in genome stability: autophagy-dependent and independent actions. Int J Biol Sci. 2022;18:5329–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Cheng SM, Shieh M, Lin T, Cheung CHA. The “dark side” of autophagy on the maintenance of genome stability: does it really exist during excessive activation?. J Cell Physiol. 2022;237:178–88.

    CAS  PubMed  Google Scholar 

  42. Miller S, Oleksy A, Perisic O, Williams RL. Finding a fitting shoe for Cinderella: searching for an autophagy inhibitor. Autophagy. 2010;6:805–07.

    PubMed  PubMed Central  Google Scholar 

  43. Lokau J, Garbers C. Activating mutations of the gp130/JAK/STAT pathway in human diseases. Adv Protein Chem Struct Biol. 2019;116:283–309.

    CAS  PubMed  Google Scholar 

  44. Wang X, Lin L, Lan B, Wang Y, Du L, Chen X, et al. IGF2r-initiated proton rechanneling dictates an anti-inflammatory property in macrophages. Sci Adv. 2020;6:eabb7389.

  45. Han YH, Moon HJ, You BR, Park WH. The effect of MG132, a proteasome inhibitor, on HeLa cells in relation to cell growth, reactive oxygen species, and GSH. Oncol Rep. 2009;22:215–21.

    CAS  PubMed  Google Scholar 

  46. Schneider-Poetsch T, Ju J, Eyler DE, Dang Y, Bhat S, Merrick WC, et al. Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycin. Nat Chem Biol. 2010;6:209–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci. 2006;31:137–55.

    CAS  PubMed  Google Scholar 

  48. Swatek KN, Komander D. Ubiquitin modifications. Cell Res. 2016;26:399–422.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Md Mokhtar AH, Malik IA, Abd Aziz NAA, Almabhouh FA, Durairajanayagam D, Singh HJ. LY294002, a PI3k pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats. Andrologia. 2019;51:e13196.

    PubMed  Google Scholar 

  50. Zhao Y, Tian Y, Zhang J, Xu F, Yang Y, Huang Y, et al. Effects of an oral allosteric AKT inhibitor (MK-2206) on human nasopharyngeal cancer in vitro and in vivo. Drug Des Dev Ther. 2014;8:1827–37.

    Google Scholar 

  51. Ferrajoli A, Faderl S, Van Q, Koch P, Harris D, Liu Z, et al. WP1066 disrupts Janus kinase-2 and induces caspase-dependent apoptosis in acute myelogenous leukemia cells. Cancer Res. 2007;67:11291–99.

    CAS  PubMed  Google Scholar 

  52. McMurray JS. A new small-molecule STAT3 inhibitor. Chem Biol. 2006;13:1123–24.

    CAS  PubMed  Google Scholar 

  53. Schindler S, Magalhães RA, Costa ELF, Brites C. Genital cytokines in HIV/human papillomavirus co-infection: a systematic review. AIDS Res Hum Retrovir. 2022;38:683–91.

    CAS  PubMed  Google Scholar 

  54. Liu H, Lyu D, Zhang Y, Sheng L, Tang N. Association between the IL-6 rs1800795 polymorphism and the risk of cervical cancer: a meta-analysis of 1210 cases and 1525 controls. Technol Cancer Res Treat. 2017;16:662–67.

    CAS  PubMed  Google Scholar 

  55. Hu F, Song D, Yan Y, Huang C, Shen C, Lan J, et al. IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation. Nat Commun. 2021;12:3651.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Kumari N, Dwarakanath BS, Das A, Bhatt AN. Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol J Int Soc Oncodev Biol Med. 2016;37:11553–72.

    CAS  Google Scholar 

  57. Wei LH, Kuo ML, Chen CA, Chou CH, Cheng WF, Chang MC, et al. The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of MCL-1 through a PI 3-k/akt pathway. Oncogene. 2001;20:5799–809.

    CAS  PubMed  Google Scholar 

  58. Das R, Bhattacharya K, Samanta SK, Pal BC, Mandal C. Improved chemosensitivity in cervical cancer to cisplatin: synergistic activity of mahanine through STAT3 inhibition. Cancer Lett. 2014;351:81–90.

    CAS  PubMed  Google Scholar 

  59. Vázquez-Mellado MJ, Cortés-Ballinas LG, Blanco-Flores IC, Aguilar C, Vázquez-Gómez G, Rocha-Zavaleta L. Erythropoietin promotes expression of survivin via STAT3 activation and reduces sensitivity to cisplatin in cervical cancer cells. Oncol Rep. 2019;41:1333–41.

    PubMed  Google Scholar 

  60. Belotte J, Fletcher NM, Awonuga AO, Alexis M, Abu-Soud HM, Saed MG, et al. The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer. Reprod Sci. 2014;21:503–08.

    PubMed  PubMed Central  Google Scholar 

  61. Bravo-Cuellar A, Ortiz-Lazareno PC, Sierra-Díaz E, Solorzano-Ibarra F, Méndez-Clemente AS, Aguilar-Lemarroy A, et al. Pentoxifylline sensitizes cisplatin-resistant human cervical cancer cells to cisplatin treatment: involvement of mitochondrial and NF-kappa b pathways. Front Oncol. 2020;10:592706.

    PubMed  PubMed Central  Google Scholar 

  62. Goto S, Yoshida K, Morikawa T, Urata Y, Suzuki K, Kondo T. Augmentation of transport for cisplatin-glutathione adduct in cisplatin-resistant cancer cells. Cancer Res. 1995;55:4297–301.

    CAS  PubMed  Google Scholar 

  63. Ceccaldi R, Rondinelli B, D’Andrea AD. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 2016;26:52–64.

    CAS  PubMed  Google Scholar 

  64. Symington LS, Gautier J. Double-strand break end resection and repair pathway choice. Annu Rev Genet. 2011;45:247–71.

    CAS  PubMed  Google Scholar 

  65. Yang S, Wang XQ. XLF-mediated NHEJ activity in hepatocellular carcinoma therapy resistance. BMC Cancer. 2017;17:344.

    PubMed  PubMed Central  Google Scholar 

  66. Zheng S, Tian Q, Yuan Y, Sun S, Li T, Xia R, et al. Extracellular vesicle-packaged circBIRC6 from cancer-associated fibroblasts induce platinum resistance via SUMOylation modulation in pancreatic cancer. J Exp Clin Cancer Res CR. 2023;42:324.

    CAS  PubMed  Google Scholar 

  67. Mi L, Cai Y, Qi J, Chen L, Li Y, Zhang S, et al. Elevated nonhomologous end-joining by AATF enables efficient DNA damage repair and therapeutic resistance in glioblastoma. Nat Commun. 2025;16:4941.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Yang J, Chatterjee-Kishore M, Staugaitis SM, Nguyen H, Schlessinger K, Levy DE, et al. Novel roles of unphosphorylated STAT3 in oncogenesis and transcriptional regulation. Cancer Res. 2005;65:939–47.

    CAS  PubMed  Google Scholar 

  69. Shi S, Ma H, Zhang Z. Clinicopathological and prognostic value of STAT3/p-STAT3 in cervical cancer: a meta and bioinformatics analysis. Pathol Res Pract. 2021;227:153624.

    CAS  PubMed  Google Scholar 

  70. Wu L, Shen B, Li J, Zhang H, Zhang K, Yang Y, et al. STAT3 exerts pro-tumor and anti-autophagy roles in cervical cancer. Diagn Pathol. 2022;17:13.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Rolén U, Kobzeva V, Gasparjan N, Ovaa H, Winberg G, Kisseljov F, et al. Activity profiling of deubiquitinating enzymes in cervical carcinoma biopsies and cell lines. Mol Carcinog. 2006;45:260–69.

    PubMed  Google Scholar 

  72. Meng Y, Hong C, Yang S, Qin Z, Yang L, Huang Y. Roles of USP9x in cellular functions and tumorigenesis (review). Oncol Lett. 2023;26:506.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Yuan Z, Chen D, Chen X, Yang H, Wei Y. Overexpression of trefoil factor 3 (TFF3) contributes to the malignant progression in cervical cancer cells. Cancer Cell Int. 2017;17:7.

    PubMed  PubMed Central  Google Scholar 

  74. Ara T, Nakata R, Sheard MA, Shimada H, Buettner R, Groshen SG, et al. Critical role of STAT3 in IL-6-mediated drug resistance in human neuroblastoma. Cancer Res. 2013;73:3852–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Liang Q, Gong M, Zou J, Luo M, Jiang L, Wang C, et al. A phosphoglycerate mutase 1 allosteric inhibitor overcomes drug resistance to EGFR-targeted therapy via disrupting IL-6/JAK2/STAT3 signaling pathway in lung adenocarcinoma. Drug Resist Updates Rev Comment Antimicrob Anticancer Chemother. 2023;68:100957.

    CAS  Google Scholar 

  76. Bubner B, Baldwin IT. Use of real-time PCR for determining copy number and zygosity in transgenic plants. Plant Cell Rep. 2004;23:263–71.

    CAS  PubMed  Google Scholar 

  77. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984:22:27–55.

  78. Olive PL, Banáth JP. The comet assay: a method to measure DNA damage in individual cells. Nat Protoc. 2006;1:23–29.

    CAS  PubMed  Google Scholar 

  79. Chaubey RC. Computerized image analysis software for the comet assay. Methods Mol Biol. 2005;291:97–106.5.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Professor Tie Wang (Institute of Intelligent Detection for Life and Health, Tianjin University of Technology) for providing the experimental platform and instruments for this research. This work was supported by the National Natural Science Foundation of China (grant number 81602403) and Tianjin Natural Science Foundation (No.23JCQNJC00790).

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  1. These authors contributed equally: Yaxin Zhang, Liping Yan.

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  1. Institute of Intelligent Detection for Life and Health, Tianjin University of Technology, Tianjin, China

    Yaxin Zhang, Liping Yan, Na An, Jiayu Geng, Wei Zhao, Bohao Feng, Yanlong Zheng, Shaojun Liang & Lei Yang

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Contributions

YXZ and LY designed the study; YXZ performed the bioinformatics experiments; YXZ and LPY performed all the experiments; NA and BHF performed the preparation of the recombinant protein TFF3; WZ and LSJ cultured the human cervical cancer cell line; YXZ and LPY performed the data processing and visualization; YXZ and LY wrote and revised the manuscript; and JYG completed the construction of the plasmid.

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Correspondence to Lei Yang.

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Zhang, Y., Yan, L., An, N. et al. TFF3 sensitizes cervical carcinoma cells to cisplatin toxicity by binding to IGF2R. Cancer Gene Ther 33, 155–168 (2026). https://doi.org/10.1038/s41417-025-00990-w

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