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Abstract

Introduction

Multidrug resistance (MDR) remains a major obstacle in the treatment of epithelial ovarian cancer (EOC). This study aimed to elucidate the regulatory role of FBXW7 in modulating the HSF-1/P-glycoprotein (P-gp) signalling axis and its impact on MDR in ovarian cancer.

Materials and Methods

Quantitative PCR, western blotting, immunohistochemistry, and immunofluorescence were employed to assess FBXW7, HSF-1, and P-gp expression in ovarian tissues and cell lines. Functional assays, including CCK-8 proliferation assays and lentiviral-mediated gene modulation, were conducted in SKOV3 and cisplatin-resistant SKOV3/DDP cells to evaluate the effects of FBXW7 on cell proliferation and drug resistance-associated pathways.

Results

FBXW7 expression was markedly reduced in ovarian cancer tissues compared to normal controls and positively correlated with patient progression-free survival. Overexpression of FBXW7 suppressed proliferation in both SKOV3 and SKOV3/DDP cells and led to decreased HSF-1 and P-gp expression. Conversely, FBXW7 knockdown enhanced cell proliferation and upregulated the HSF-1/P-gp axis. Immunohistochemical and immunofluorescence analyses confirmed an inverse expression pattern between FBXW7 and HSF-1 in patient tissues.

Discussion

The findings revealed FBXW7 to suppress multidrug resistance in ovarian cancer by downregulating the HSF-1/P-gp axis, thereby enhancing chemosensitivity. This study has highlighted a novel regulatory mechanism and suggested that restoring FBXW7 function may offer therapeutic benefit in overcoming chemoresistance.

Conclusion

FBXW7 acts as a tumour suppressor that mitigates MDR in ovarian cancer by negatively regulating the HSF-1/P-gp pathway. The findings have offered mechanistic insights into chemoresistance and highlight the therapeutic potential of targeting FBXW7-HSF-1 signalling in EOC management.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2026-01-12
2026-01-31

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References

  1. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  2. Seoud M. Ladjeroud A. Jaafar H. Mokhtar M. Ozyilkan O. Alkhayyat S. Dawood S. Arik Z. Azim H.A. Frontline management of advanced epithelial ovarian cancer: A comprehensive statement by the Africa Middle East Cancer Inter-group. Curr. Womens Health Rev. 2023 20 1 e211022210275 e211022210275 [AMCI]. [http://dx.doi.org/10.2174/1573404819666221021091708
    [Google Scholar]
  3. Guo Y. Chen X. Tang X. Pan S. Zhu T. Zhang Y. Real-world study on the effect of PARPi as maintenance therapy on platinum sensitivity after first- and second-line chemotherapy in patients with recurrent high-grade serous epithelial ovarian cancer. Curr. Cancer Drug Targets 2024 24 7 733 748 10.2174/0115680096271476231226174810 38173064
    [Google Scholar]
  4. Babaoglu S. Atas A.E. Kerimoglu U. İyisoy M.S. Kilinc F. Differentiation of borderline epithelial ovarian tumors from benign and malignant epithelial ovarian tumors by MRI scoring. Curr. Med. Imaging 2023 20 e060623217706 10.2174/1573405620666230606125445 37282660
    [Google Scholar]
  5. Caruso G. Weroha S.J. Cliby W. Ovarian cancer: A review. JAMA 2025 334 14 1278 1291 10.1001/jama.2025.9495 40690248
    [Google Scholar]
  6. Xie B. Zhou X. Luo C. Fang Y. Wang Y. Wei J. Cai L. Chen T. Reversal of platinum-based chemotherapy resistance in ovarian cancer by naringin through modulation of the gut microbiota in a humanized nude mouse model. J. Cancer 2024 15 13 4430 4447 10.7150/jca.96448 38947385
    [Google Scholar]
  7. Zhou X. Hu G. Luo Z. Luo C. Wei J. Wang X. Shen Z. Yu Y. Chen T. Cai L. Probiotics alleviate paraneoplastic thrombocythemia of ovarian cancer: A randomized placebo-controlled trial. J. Funct. Foods 2024 119 106316 10.1016/j.jff.2024.106316
    [Google Scholar]
  8. Zhou X. Yu Y. Xie B. Chen T. Cai L. Naringin regulates the growth and apoptosis of ovarian cancer cells via the TGF-β signaling pathway: A prospective laboratory based study. Clin. Exp. Obstet. Gynecol. 2024 51 5 111 10.31083/j.ceog5105111
    [Google Scholar]
  9. Ye C. Hu G. Zhou X. Deng W. Hu K. Fu M. Comparative analysis of gene expression profiles in ovarian clear cell carcinoma and high-grade serous ovarian cancer. J. Coll. Physicians Surg. Pak. 2024 34 9 1066 1072 10.29271/jcpsp.2024.09.1066 39262007
    [Google Scholar]
  10. Gong P. Li J. Zhang Y. Zhang S. Immunogenic cell death-relevant molecular patterns, prognostic genes, and implications for immunotherapy in ovarian cancer. Curr. Med. Chem. 2025 32 10.2174/0109298673354860250220065131 40183271
    [Google Scholar]
  11. Raeisi E. Heidari-Soureshjani S. Mt Sherwin C. Bagheri Z. Radiotherapy enhancing and radioprotective properties of berberine: A systematic review. Recent Pat. Anticancer Drug Discov 2024 10.2174/0115748928315442240624120104 38984581
    [Google Scholar]
  12. Adib-Hajbagheri P. Rafiyian M. Ataee S. Rafi A. Farkhondeh T. Samini M. Pourhanifeh M.H. Samarghandian S. Protective effects of ginsenosides on drug-induced cardiotoxicity: A new therapeutic approach with focus on molecular mechanisms in cardio-oncology field. Curr. Med. Chem. 2025 32 10.2174/0109298673327575250331145643 40248929
    [Google Scholar]
  13. Gu Z. Inomata K. Ishizawa K. Horii A. The FBXW7 β-form is suppressed in human glioma cells. Biochem. Biophys. Res. Commun. 2007 354 4 992 998 10.1016/j.bbrc.2007.01.080 17274947
    [Google Scholar]
  14. Kitade S. Onoyama I. Kobayashi H. Yagi H. Yoshida S. Kato M. Tsunematsu R. Asanoma K. Sonoda K. Wake N. Hata K. Nakayama K.I. Kato K. FBXW7 is involved in the acquisition of the malignant phenotype in epithelial ovarian tumors. Cancer Sci. 2016 107 10 1399 1405 10.1111/cas.13026 27486687
    [Google Scholar]
  15. Zhu Q. Hu L. Guo Y. Xiao Z. Xu Q. Tong X. FBW7 in hematological tumors (Review). Oncol. Lett. 2020 19 3 1657 1664 10.3892/ol.2020.11264 32194657
    [Google Scholar]
  16. Qi Y. Rezaeian A.H. Wang J. Huang D. Chen H. Inuzuka H. Wei W. Molecular insights and clinical implications for the tumor suppressor role of SCFFBXW7 E3 ubiquitin ligase. Biochim. Biophys. Acta Rev. Cancer 2024 1879 5 189140 10.1016/j.bbcan.2024.189140 38909632
    [Google Scholar]
  17. Motomura S. Yumimoto K. Tomonaga T. Nakayama K.I. CRL2KLHDC3 and CRL1Fbxw7 cooperatively mediate c-Myc degradation. Oncogene 2024 43 25 1917 1929 10.1038/s41388‑024‑03048‑7 38698266
    [Google Scholar]
  18. Sakamoto Y. Ishida T. Masaki A. Murase T. Ohtsuka E. Takeshita M. Muto R. Choi I. Iwasaki H. Ito A. Kusumoto S. Nakano N. Tokunaga M. Yonekura K. Tashiro Y. Suehiro Y. Iida S. Utsunomiya A. Ueda R. Inagaki H. Clinical significance of NOTCH1 and FBXW7 alterations in adult T-cell leukemia/lymphoma. Int. J. Hematol. 2025 121 2 206 221 10.1007/s12185‑024‑03880‑3 39586983
    [Google Scholar]
  19. Al Hinai M. Malgundkar S. Gupta I. Lakhtakia R. Al Kalbani M. Burney I. Al Moundhri M. Okamoto A. Tamimi Y. Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis. Asian Pac. J. Cancer Prev. 2023 24 5 1583 1590 10.31557/APJCP.2023.24.5.1583 37247277
    [Google Scholar]
  20. Sachdeva A. Roy A. Gupta M.K. Mandal S. Pharmacological inhibition of protein kinase D2/Aurora kinase A signalling axis suppresses G2/M cell cycle progression and proliferation of epithelial ovarian cancer cells. Pathol. Res. Pract. 2024 260 155390 10.1016/j.prp.2024.155390 38878668
    [Google Scholar]
  21. Despierre E. Yesilyurt B.T. Lambrechts S. Johnson N. Verheijen R. van der Burg M. Casado A. Rustin G. Berns E. Leunen K. Amant F. Moerman P. Lambrechts D. Vergote I. Epithelial ovarian cancer: Rationale for changing the one-fits-all standard treatment regimen to subtype-specific treatment. Int. J. Gynecol. Cancer 2014 24 3 468 477 10.1097/IGC.0000000000000089 24557434
    [Google Scholar]
  22. Zhong L. Pan Y. Shen J. FBXW7 inhibits invasion, migration and angiogenesis in ovarian cancer cells by suppressing VEGF expression through inactivation of β-catenin signaling. Exp. Ther. Med. 2021 21 5 514 10.3892/etm.2021.9945 33791023
    [Google Scholar]
  23. Suda K. Nakaoka H. Yoshihara K. Ishiguro T. Tamura R. Mori Y. Yamawaki K. Adachi S. Takahashi T. Kase H. Tanaka K. Yamamoto T. Motoyama T. Inoue I. Enomoto T. Clonal expansion and diversification of cancer-associated mutations in endometriosis and normal endometrium. Cell Rep. 2018 24 7 1777 1789 10.1016/j.celrep.2018.07.037 30110635
    [Google Scholar]
  24. Halling G.C. Udager A.M. Skala S.L. Endometrial, ovarian, and peritoneal involvement by endometrioid carcinoma, yolk sac tumor, and endometriosis: Molecular evidence for a shared precursor. Int. J. Gynecol. Pathol. 2023 42 3 247 253 10.1097/PGP.0000000000000889 35639393
    [Google Scholar]
  25. Zhong L. Pan Y. Shen J. FBXW7 inhibits invasion, migration and angiogenesis in ovarian cancer cells by suppressing VEGF expression through inactivation of β catenin signaling. Exp. Ther. Med. 2021 21 5 514 10.3892/etm.2021.9945 33791023
    [Google Scholar]
  26. Wang M. Li Y. Xiao Y. Yang M. Chen J. Jian Y. Chen X. Shi D. Chen X. Ouyang Y. Kong L. Huang X. Bai J. Lin C. Song L. Nicotine-mediated OTUD3 downregulation inhibits VEGF-C mRNA decay to promote lymphatic metastasis of human esophageal cancer. Nat. Commun. 2021 12 1 7006 10.1038/s41467‑021‑27348‑8 34853315
    [Google Scholar]
  27. Tian X. Liu Y. Wang Z. Wu S. miR-144 delivered by nasopharyngeal carcinoma-derived EVs stimulates angiogenesis through the FBXW7/HIF-1α/VEGF-A axis. Mol. Ther. Nucleic Acids 2021 24 1000 1011 10.1016/j.omtn.2021.03.016 34094717
    [Google Scholar]
  28. Hu L. Lv X. Li D. Zhang W. Ran G. Li Q. Hu J. The anti‐angiogenesis role of FBXW7 in diabetic retinopathy by facilitating the ubiquitination degradation of c‐Myc to orchestrate the HDAC2. J. Cell. Mol. Med. 2021 25 4 2190 2202 10.1111/jcmm.16204 33369138
    [Google Scholar]
  29. Sanchez-Burgos L. Navarro-González B. García-Martín S. Sirozh O. Mota-Pino J. Fueyo-Marcos E. Tejero H. Antón M.E. Murga M. Al-Shahrour F. Fernandez-Capetillo O. Activation of the integrated stress response is a vulnerability for multidrug‐resistant FBXW7‐deficient cells. EMBO Mol. Med. 2022 14 9 e15855 10.15252/emmm.202215855 35861150
    [Google Scholar]
  30. Stephenson S.E.M. Costain G. Blok L.E.R. Silk M.A. Nguyen T.B. Dong X. Alhuzaimi D.E. Dowling J.J. Walker S. Amburgey K. Hayeems R.Z. Rodan L.H. Schwartz M.A. Picker J. Lynch S.A. Gupta A. Rasmussen K.J. Schimmenti L.A. Klee E.W. Niu Z. Agre K.E. Chilton I. Chung W.K. Revah-Politi A. Au P.Y.B. Griffith C. Racobaldo M. Raas-Rothschild A. Ben Zeev B. Barel O. Moutton S. Morice-Picard F. Carmignac V. Cornaton J. Marle N. Devinsky O. Stimach C. Wechsler S.B. Hainline B.E. Sapp K. Willems M. Bruel A. Dias K.R. Evans C.A. Roscioli T. Sachdev R. Temple S.E.L. Zhu Y. Baker J.J. Scheffer I.E. Gardiner F.J. Schneider A.L. Muir A.M. Mefford H.C. Crunk A. Heise E.M. Millan F. Monaghan K.G. Person R. Rhodes L. Richards S. Wentzensen I.M. Cogné B. Isidor B. Nizon M. Vincent M. Besnard T. Piton A. Marcelis C. Kato K. Koyama N. Ogi T. Goh E.S.Y. Richmond C. Amor D.J. Boyce J.O. Morgan A.T. Hildebrand M.S. Kaspi A. Bahlo M. Friðriksdóttir R. Katrínardóttir H. Sulem P. Stefánsson K. Björnsson H.T. Mandelstam S. Morleo M. Mariani M. Scala M. Accogli A. Torella A. Capra V. Wallis M. Jansen S. Waisfisz Q. de Haan H. Sadedin S. Lim S.C. White S.M. Ascher D.B. Schenck A. Lockhart P.J. Christodoulou J. Tan T.Y. Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome. Am. J. Hum. Genet. 2022 109 4 601 617 10.1016/j.ajhg.2022.03.002 35395208
    [Google Scholar]
  31. Chen S. Leng P. Guo J. Zhou H. FBXW7 in breast cancer: Mechanism of action and therapeutic potential. J. Exp. Clin. Cancer Res. 2023 42 1 226 10.1186/s13046‑023‑02767‑1 37658431
    [Google Scholar]
  32. Sato Y. Habara M. Hanaki S. Masaki T. Tomiyasu H. Miki Y. Sakurai M. Morimoto M. Kobayashi D. Miyamoto T. Shimada M. Calcineurin-mediated dephosphorylation stabilizes E2F1 protein by suppressing binding of the FBXW7 ubiquitin ligase subunit. Proc. Natl. Acad. Sci. USA 2024 121 41 e2414618121 10.1073/pnas.2414618121 39361641
    [Google Scholar]
  33. Escobar D. Bushara O. Sun L. Liao J. Yang G.Y. Clinicopathologic characteristics of FBXW7-mutated colorectal adenocarcinoma and association with aberrant beta-catenin localization. Hum. Pathol. 2022 119 51 58 10.1016/j.humpath.2021.10.003 34717891
    [Google Scholar]
  34. Kar R. Jha S.K. Ojha S. Sharma A. Dholpuria S. Raju V.S.R. Prasher P. Chellappan D.K. Gupta G. Kumar Singh S. Paudel K.R. Hansbro P.M. Kumar Singh S. Ruokolainen J. Kesari K.K. Dua K. Jha N.K. The FBXW7‐NOTCH interactome: A ubiquitin proteasomal system‐induced crosstalk modulating oncogenic transformation in human tissues. Cancer Rep. 2021 4 4 e1369 10.1002/cnr2.1369 33822486
    [Google Scholar]
  35. Sun Y. Xu M. Wan H.L. Ding X. Wong A.M. Pu D. Ng K.K. Wong N. Spliced exon9 ADRM1 promotes liver oncogenicity via selective degradation of tumor suppressor FBXW7. J. Hepatol. 2025 83 1 92 104 10.1016/j.jhep.2024.12.037 39788431
    [Google Scholar]
  36. Li J. Jia K. Wang W. Pang Y. Wang H. Hao J. Zhao D. Li F. FBXW7 mediates high glucose-induced epithelial to mesenchymal transition via KLF5 in renal tubular cells of diabetic kidney disease. Tissue Cell 2025 94 102801 10.1016/j.tice.2025.102801 40010183
    [Google Scholar]
  37. Li X. Liu J. Zhou Y. Wang L. Wen Y. Ding K. Zou L. Liu X. Li A. Wang Y. Fu H. Huang M. Ding G. Zhou J. Jwa participates the maintenance of intestinal epithelial homeostasis via ERK/FBXW7-mediated NOTCH1/PPARγ/STAT5 axis and acts as a novel putative aging related gene. Int. J. Biol. Sci. 2022 18 14 5503 5521 10.7150/ijbs.72751 36147468
    [Google Scholar]
  38. He H. Liu L. Zhang S. Zheng M. Ma A. Chen Z. Pan H. Zhou H. Liang R. Cai L. Smart gold nanocages for mild heat-triggered drug release and breaking chemoresistance. J. Control. Release 2020 323 387 397 10.1016/j.jconrel.2020.04.029 32330573
    [Google Scholar]
  39. Krishnamurthy K. Glaser S. Alpini G.D. Cardounel A.J. Liu Z. Ilangovan G. Heat shock factor-1 knockout enhances cholesterol 7α-hydroxylase (CYP7A1) and multidrug transporter (MDR1) gene expressions to attenuate atherosclerosis. Cardiovasc. Res. 2016 111 1 74 83 10.1093/cvr/cvw094 27131506
    [Google Scholar]
  40. Krishnamurthy K. Vedam K. Kanagasabai R. Druhan L.J. Ilangovan G. Heat shock factor-1 knockout induces multidrug resistance gene, MDR1b, and enhances P-glycoprotein (ABCB1)-based drug extrusion in the heart. Proc. Natl. Acad. Sci. USA 2012 109 23 9023 9028 10.1073/pnas.1200731109 22615365
    [Google Scholar]
  41. Moon H.J. Kim H.B. Lee S.H. Jeun S.E. Kang C.D. Kim S.H. Sensitization of multidrug-resistant cancer cells to Hsp90 inhibitors by NSAIDs-induced apoptotic and autophagic cell death. Oncotarget 2018 9 13 11303 11321 10.18632/oncotarget.24130 29541415
    [Google Scholar]
  42. Wu Q. Hossfeld A. Gerberick A. Saljoughian N. Tiwari C. Mehra S. Ganesan L.P. Wozniak D.J. Rajaram M.V.S. Effect of mycobacterium tuberculosis enhancement of macrophage p-glycoprotein expression and activity on intracellular survival during antituberculosis drug treatment. J. Infect. Dis. 2019 220 12 1989 1998 10.1093/infdis/jiz405 31412123
    [Google Scholar]
  43. Mun G.I. Choi E. Lee Y. Lee Y.S. Decreased expression of FBXW7 by ERK1/2 activation in drug-resistant cancer cells confers transcriptional activation of MDR1 by suppression of ubiquitin degradation of HSF1. Cell Death Dis. 2020 11 5 395 10.1038/s41419‑020‑2600‑3 32457290
    [Google Scholar]
  44. Liu Z. Lin Z. Jiang M. Zhu G. Xiong T. Cao F. Cui Y. Niu Y.N. Cancer-associated fibroblast exosomes promote prostate cancer metastasis through miR-500a-3p/FBXW7/HSF1 axis under hypoxic microenvironment. Cancer Gene Ther. 2024 31 5 698 709 10.1038/s41417‑024‑00742‑2 38351137
    [Google Scholar]
  45. Kourtis N. Moubarak R.S. Aranda-Orgilles B. Lui K. Aydin I.T. Trimarchi T. Darvishian F. Salvaggio C. Zhong J. Bhatt K. Chen E.I. Celebi J.T. Lazaris C. Tsirigos A. Osman I. Hernando E. Aifantis I. FBXW7 modulates cellular stress response and metastatic potential through HSF1 post-translational modification. Nat. Cell Biol. 2015 17 3 322 332 10.1038/ncb3121 25720964
    [Google Scholar]
  46. Xu J. Shi Q. Xu W. Zhou Q. Shi R. Ma Y. Chen D. Zhu L. Feng L. Cheng A.S.L. Morrison H. Wang X. Jin H. Metabolic enzyme PDK3 forms a positive feedback loop with transcription factor HSF1 to drive chemoresistance. Theranostics 2019 9 10 2999 3013 10.7150/thno.31301 31244938
    [Google Scholar]
  47. Gomez-Pastor R. Burchfiel E.T. Neef D.W. Jaeger A.M. Cabiscol E. McKinstry S.U. Doss A. Aballay A. Lo D.C. Akimov S.S. Ross C.A. Eroglu C. Thiele D.J. Abnormal degradation of the neuronal stress-protective transcription factor HSF1 in Huntington’s disease. Nat. Commun. 2017 8 1 14405 10.1038/ncomms14405 28194040
    [Google Scholar]
  48. Lee Y.Y. Jeon H.K. Hong J.E. Cho Y.J. Ryu J.Y. Choi J.J. Lee S.H. Yoon G. Kim W.Y. Do I.G. Kim M.K. Kim T.J. Choi C.H. Lee J.W. Bae D.S. Kim B.G. Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma. Oncotarget 2015 6 33 35040 35050 10.18632/oncotarget.5319 26418900
    [Google Scholar]
  49. Kim W.J. Ryu J.Y. Chang C.S. Cho Y.J. Choi J.J. Hwang J.R. Choi J.Y. Lee J.W. Anticancer effect of the antipsychotic agent penfluridol on epithelial ovarian cancer. J. Gynecol. Oncol. 2025 36 2 e28 10.3802/jgo.2025.36.e28 39223944
    [Google Scholar]
  50. Gandham S.K. Rao M. Shah A. Trivedi M.S. Amiji M.M. Combination microRNA-based cellular reprogramming with paclitaxel enhances therapeutic efficacy in a relapsed and multidrug-resistant model of epithelial ovarian cancer. Mol. Ther. Oncolytics 2022 25 57 68 10.1016/j.omto.2022.03.005 35399604
    [Google Scholar]
  51. Zhang X. Wang J. Liu N. Wu W. Li H. Chen J. Guo X. Molecular mechanism of CD163+ tumor-associated macrophage (TAM)-derived exosome-induced cisplatin resistance in ovarian cancer ascites. Ann. Transl. Med. 2022 10 18 1014 10.21037/atm‑22‑4267 36267748
    [Google Scholar]
  52. Boerner T. Zivanovic O. Chi D.S. Narrative review of cytoreductive surgery and intraperitoneal chemotherapy for peritoneal metastases in ovarian cancer. J. Gastrointest. Oncol. 2021 12 S1 S137 S143 10.21037/jgo‑20‑274 33968434
    [Google Scholar]
  53. Mittica G. Ghisoni E. Giannone G. Genta S. Aglietta M. Sapino A. Valabrega G. PARP inhibitors in ovarian cancer. Recent Patents Anticancer Drug Discov. 2018 13 4 392 410 10.2174/1574892813666180305165256 29512470
    [Google Scholar]
  54. Elyashiv O. Wong Y.N.S. Ledermann J.A. Frontline maintenance treatment for ovarian cancer. Curr. Oncol. Rep. 2021 23 8 97 10.1007/s11912‑021‑01088‑w 34125335
    [Google Scholar]
  55. Goldlust I.S. Guidice E. Lee J. PARP inhibitors in ovarian cancer. Semin. Oncol. 2024 51 1-2 45 57 10.1053/j.seminoncol.2024.01.001 38262776
    [Google Scholar]
  56. Xu F. Li J. Ni M. Cheng J. Zhao H. Wang S. Zhou X. Wu X. FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2. Mol. Cancer 2021 20 1 45 10.1186/s12943‑021‑01340‑8 33658012
    [Google Scholar]
  57. Peng Y. Wang P. Lou Y. Wang D. Mechanism of FBXW7 mRNA degradation mediated by circSMAD2 through METTL3-METTL14 m6A axis affects proliferation and invasion of endometrial stromal cells. J. Reprod. Immunol. 2025 169 104523 10.1016/j.jri.2025.104523 40184726
    [Google Scholar]
  58. Ashley C.W. Da Cruz Paula A. Ferrando L. Gularte-Mérida R. Sebastiao A.P.M. Brown D.N. Gazzo A.M. Pareja F. Stylianou A. Abu-Rustum N.R. Reis-Filho J.S. Buehler D. Weisman P. Chiang S. Weigelt B. Genetic characterisation of adult primary pleomorphic uterine rhabdomyosarcoma and comparison with uterine carcinosarcoma. Histopathology 2021 79 2 176 186 10.1111/his.14346 33527450
    [Google Scholar]
  59. Wei X. Feng J. Chen L. Zhang C. Liu Y. Zhang Y. Xu Y. Zhang J. Wang J. Yang H. Han X. Wang G. METTL3-mediated m6A modification of LINC00520 confers glycolysis and chemoresistance in osteosarcoma via suppressing ubiquitination of ENO1. Cancer Lett. 2025 611 217194 10.1016/j.canlet.2024.217194 39168299
    [Google Scholar]
  60. Guo Y. Zhang Z. Wang Z. Liu G. Liu Y. Wang H. Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway. Biosci. Rep. 2020 40 3 BSR20193396 10.1042/BSR20193396 32159214
    [Google Scholar]
  61. Miao S. Wang J. Xuan L. Liu X. LncRNA TTN‐AS1 acts as sponge for miR‐15b‐5p to regulate FBXW7 expression in ovarian cancer. Biofactors 2020 46 4 600 607 10.1002/biof.1622 32049388
    [Google Scholar]
  62. Liu T. Yuan L. Zou X. Circular RNA circ-BNC2 (hsa_circ_0008732) inhibits the progression of ovarian cancer through microRNA-223-3p/ FBXW7 axis. J. Ovarian Res. 2022 15 1 95 10.1186/s13048‑022‑01025‑w 35965327
    [Google Scholar]
  63. Lu B. Feng Z. Fan B. Shi Y. Blocking miR-27a-3p sensitises Taxol resistant osteosarcoma cells through targeting Fbxw7. Bull. Cancer 2021 108 6 596 604 10.1016/j.bulcan.2021.01.006 33863546
    [Google Scholar]
  64. Yu C. Qiu M. Xiong X. Peng H. Han S. Song X. Hu C. Zhang Z. Xia B. Chen J. Zhu S. Yang L. Li W. Yin H. Zhao J. Lin Z. Liu Y. Yang C. Integrative analysis of RNA-seq and Ribo-seq reveals that lncRNA-GRN regulates chicken follicular atresia through miR-103-3p/FBXW7 axis and encoding peptide. Int. J. Biol. Macromol. 2024 278 Pt 4 135051 10.1016/j.ijbiomac.2024.135051 39182874
    [Google Scholar]
  65. Wang G. Zhu Y. Liu Y. Yang M. Zeng L. Mesenchymal stem cells-derived exosomal miR-223-3p alleviates ocular surface damage and inflammation by downregulating Fbxw7 in dry eye models. Invest. Ophthalmol. Vis. Sci. 2024 65 12 1 10.1167/iovs.65.12.1 39352716
    [Google Scholar]
  66. Cassavaugh J.M. Hale S.A. Wellman T.L. Howe A.K. Wong C. Lounsbury K.M. Negative regulation of HIF-1α by an FBW7-mediated degradation pathway during hypoxia. J. Cell. Biochem. 2011 112 12 3882 3890 10.1002/jcb.23321 21964756
    [Google Scholar]
  67. Tan W. Zhao H. Zhang F. Li Z. Feng D. Li Y. Zhou W. Liu L. Yao J. Tian X. Inhibition of the ubiquitination of HSF1 by FBXW7 protects the intestine against ischemia–reperfusion injury. Apoptosis 2018 23 11-12 667 678 10.1007/s10495‑018‑1484‑5 30284149
    [Google Scholar]
  68. Mansky R.H. Greguske E.A. Yu D. Zarate N. Intihar T.A. Tsai W. Brown T.G. Thayer M.N. Kumar K. Gomez-Pastor R. Tumor suppressor p53 regulates heat shock factor 1 protein degradation in Huntington’s disease. Cell Rep. 2023 42 3 112198 10.1016/j.celrep.2023.112198 36867535
    [Google Scholar]
  69. Cho E. Grim J.E.A. (heat) shocking development: FBXW7 loss unleashes HSF1 to drive melanoma invasion and metastasis. Pigment Cell Melanoma Res. 2015 28 6 643 644 10.1111/pcmr.12395 26178611
    [Google Scholar]
  70. Liu J. Wang H. Wan H. Yang J. Gao L. Wang Z. Zhang X. Han W. Peng J. Yang L. Hong L. NEK6 dampens FOXO3 nuclear translocation to stabilize C-MYC and promotes subsequent de novo purine synthesis to support ovarian cancer chemoresistance. Cell Death Dis. 2024 15 9 661 10.1038/s41419‑024‑07045‑2 39256367
    [Google Scholar]
  71. Hu Z. Wu Y. Sun X. Tong Y. Qiu H. Zhuo E. ARMCX1 inhibits lung adenocarcinoma progression by recruiting FBXW7 for c-Myc degradation. Biol. Direct 2024 19 1 82 10.1186/s13062‑024‑00532‑8 39285446
    [Google Scholar]
  72. Li Y. Su Y. Zhao Y. Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c-Myc axis in gastric cancer. MedComm 2021 2 3 467 480 10.1002/mco2.73
    [Google Scholar]
  73. Mo X. Shen X. Mo X. Yu F. Tan W. Deng Z. He J. Luo Z. Chen Z. Yang J. CEMIP promotes small cell lung cancer proliferation by activation of glutamine metabolism via FBXW7/c-Myc-dependent axis. Biochem. Pharmacol. 2023 209 115446 10.1016/j.bcp.2023.115446 36746261
    [Google Scholar]
  74. Han F. Qi G. Li R. Peng J. Yan S. Yuan C. Kong B. Ma H. USP28 promotes PARP inhibitor resistance by enhancing SOX9-mediated DNA damage repair in ovarian cancer. Cell Death Dis. 2025 16 1 305 10.1038/s41419‑025‑07647‑4 40240356
    [Google Scholar]
  75. Li S. Deng J. Sun D. Chen S. Yao X. Wang N. Zhang J. Gu Q. Zhang S. Wang J. Zhu S. Zhu H. Li H. Xu X. Wei F. FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition. Redox Biol. 2022 58 102530 10.1016/j.redox.2022.102530 36427396
    [Google Scholar]
  76. Patel S. Jenkins E. Kusurkar R.P. Lee S. Jiang W. Nevler A. McCoy M. Pishvaian M.J. Sears R.C. Brody J.R. Yeo C.J. Jain A. Targeting BARD1 suppresses a Myc-dependent transcriptional program and tumor growth in pancreatic ductal adenocarcinoma. Neoplasia 2025 63 101152 10.1016/j.neo.2025.101152 40096771
    [Google Scholar]
  77. Attiyeh E.F. Maris J.M. Lock R. Reynolds C.P. Kang M.H. Carol H. Gorlick R. Kolb E.A. Keir S.T. Wu J. Landesman Y. Shacham S. Lyalin D. Kurmasheva R.T. Houghton P.J. Smith M.A. Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT‐330): A report from the pediatric preclinical testing program. Pediatr. Blood Cancer 2016 63 2 276 286 10.1002/pbc.25727 26398108
    [Google Scholar]
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Regulation of HSF-1 by FBXW7 to Alleviate Multidrug Resistance in Ovarian Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0115680096427366251126115802
/content/journals/ccdt/10.2174/0115680096427366251126115802
/content/journals/ccdt/10.2174/0115680096427366251126115802
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  • Article Type:     Research Article
Keywords: FBXW7 ; chemoresistance ; E3 ubiquitin ligase ; ovarian cancer ; HSF-1 ; Multidrug resistance ; P-gp

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