Fusobacterium periodonticum BCT protein targeting glucose metabolism to promote the epithelial-mesenchymal transition of esophageal cancer cells by lactic acid.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central, 2003-
    • Subject Terms:
      Esophageal Neoplasms*/pathology ; Esophageal Neoplasms*/metabolism ; Epithelial-Mesenchymal Transition* ; Lactic Acid*/metabolism ; Glucose*/metabolism ; Cell Movement* ; Fusobacterium*/metabolism; Humans ; Cell Line, Tumor ; Bacterial Proteins/metabolism ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic
    • Abstract:
      Background: The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC.
      Methods: We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes.
      Results: Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and β-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells.
      Conclusion: Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/β-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.
      (© 2024. The Author(s).)
    • References:
      Cancer Commun (Lond). 2023 Feb;43(2):225-245. (PMID: 36346061)
      CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
      Appl Microbiol Biotechnol. 2022 Apr;106(8):3215-3229. (PMID: 35435458)
      Biomed Pharmacother. 2017 May;89:918-925. (PMID: 28292019)
      Biochem Biophys Res Commun. 2018 Sep 18;503(4):2226-2233. (PMID: 29953852)
      Life Sci. 2015 Aug 1;134:49-55. (PMID: 26037398)
      Mol Pharmacol. 2011 Nov;80(5):848-58. (PMID: 21862690)
      Life Sci. 2023 Jan 1;312:121215. (PMID: 36414093)
      Med Res Rev. 2023 Jul;43(4):1141-1200. (PMID: 36929669)
      J Infect. 2021 Mar;82(3):e42-e44. (PMID: 33248222)
      Nat Commun. 2024 Feb 24;15(1):1688. (PMID: 38402201)
      NPJ Biofilms Microbiomes. 2023 May 1;9(1):23. (PMID: 37127667)
      Cell Death Dis. 2021 Nov 20;12(12):1094. (PMID: 34799549)
      J Exp Clin Cancer Res. 2018 Feb 26;37(1):39. (PMID: 29482580)
      Signal Transduct Target Ther. 2022 Sep 1;7(1):305. (PMID: 36050306)
      Front Oncol. 2022 Jul 18;12:931104. (PMID: 35924168)
      Trends Endocrinol Metab. 2024 Mar 6;:. (PMID: 38453603)
      Cell Death Dis. 2022 Sep 3;13(9):765. (PMID: 36057597)
      Eur Rev Med Pharmacol Sci. 2016 Dec;20(24):5067-5076. (PMID: 28051265)
      NPJ Biofilms Microbiomes. 2022 Oct 29;8(1):87. (PMID: 36307484)
      Oncogene. 2023 Jul;42(29):2237-2248. (PMID: 37344626)
      Pharmacol Ther. 2020 Feb;206:107451. (PMID: 31836453)
      Front Oncol. 2020 Nov 10;10:557730. (PMID: 33244454)
      Future Med Chem. 2013 May;5(8):961-78. (PMID: 23682571)
      Semin Cancer Biol. 2022 Dec;87:184-195. (PMID: 36371026)
      Curr Med Chem. 2016;23(20):2159-87. (PMID: 27048343)
      Epidemiol Infect. 2023 Apr 03;151:e69. (PMID: 37009715)
      Sci Rep. 2024 Mar 14;14(1):6200. (PMID: 38486026)
      Polymers (Basel). 2020 Mar 06;12(3):. (PMID: 32155695)
      Int J Mol Sci. 2022 Mar 22;23(7):. (PMID: 35408801)
      Nutr Metab Cardiovasc Dis. 2023 Jan;33(1):38-46. (PMID: 36428186)
      Cell Host Microbe. 2018 Dec 12;24(6):833-846.e6. (PMID: 30543778)
      Cancer Res. 2011 Nov 15;71(22):6921-5. (PMID: 22084445)
      Microb Pathog. 2012 Aug;53(2):66-73. (PMID: 22575887)
      Biomed Res Int. 2020 Oct 31;2020:4712498. (PMID: 33204698)
      Cancer Cell. 2003 Oct;4(4):257-62. (PMID: 14585353)
      J Gastrointest Oncol. 2022 Apr;13(2):499-509. (PMID: 35557578)
      Nat Rev Clin Oncol. 2022 Oct;19(10):656-673. (PMID: 36068272)
      J Exp Clin Cancer Res. 2022 Nov 24;41(1):330. (PMID: 36419136)
      Cell Host Microbe. 2016 Aug 10;20(2):215-25. (PMID: 27512904)
      J Pathol. 2005 Mar;205(4):530-6. (PMID: 15714461)
      CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. (PMID: 38230766)
      J Ethnopharmacol. 2024 Jun 28;328:117932. (PMID: 38382652)
      Cells. 2019 Aug 21;8(9):. (PMID: 31438645)
      Blood. 2022 Nov 3;140(18):1972-1982. (PMID: 35984906)
      NPJ Biofilms Microbiomes. 2023 Aug 23;9(1):59. (PMID: 37612266)
      Phytomedicine. 2012 Jun 15;19(8-9):779-87. (PMID: 22483553)
      Trends Microbiol. 2023 Feb;31(2):159-172. (PMID: 36058786)
      Sci China Life Sci. 2024 Apr;67(4):711-719. (PMID: 38155276)
      World J Gastroenterol. 2011 Aug 28;17(32):3745-51. (PMID: 21990957)
      Proc Natl Acad Sci U S A. 2019 Jan 2;116(1):52-57. (PMID: 30559182)
      Pathogens. 2022 Jul 28;11(8):. (PMID: 36014967)
      J Immunol. 2007 Aug 15;179(4):2501-8. (PMID: 17675512)
      Semin Cancer Biol. 2023 Oct;95:1-12. (PMID: 37364663)
      Arch Biochem Biophys. 2016 May 15;598:50-6. (PMID: 27040384)
      Sci Rep. 2022 Apr 15;12(1):6261. (PMID: 35428832)
      Curr Mol Med. 2018;18(6):343-351. (PMID: 30411685)
      Curr Oncol Rep. 2024 Apr;26(4):391-399. (PMID: 38502418)
      Food Funct. 2016 Feb;7(2):843-54. (PMID: 26673746)
      Exp Mol Med. 2023 Jul;55(7):1357-1370. (PMID: 37394582)
      Clin Chim Acta. 2021 Nov;522:61-69. (PMID: 34400170)
      mBio. 2019 Jul 16;10(4):. (PMID: 31311881)
      Immunity. 2015 Feb 17;42(2):344-355. (PMID: 25680274)
      Sci Rep. 2015 Oct 14;5:15203. (PMID: 26462879)
      Front Immunol. 2021 May 21;12:658681. (PMID: 34093546)
    • Grant Information:
      82173479 National Natural Science Foundation of China; KYCX22-0303 Postgraduate Research & Practice Innovation Program of Jiangsu Province
    • Contributed Indexing:
      Keywords: EMT; Esophageal cancer; Fusobacterium periodonticum; Glycolysi; TLR4/Akt/HIF-1α
    • Accession Number:
      33X04XA5AT (Lactic Acid)
      IY9XDZ35W2 (Glucose)
      0 (Bacterial Proteins)
    • Publication Date:
      Date Created: 20240430 Date Completed: 20240501 Latest Revision: 20240503
    • Publication Date:
      20240503
    • Accession Number:
      PMC11061911
    • Accession Number:
      10.1186/s12967-024-05157-z
    • Accession Number:
      38689341