Akkermansia muciniphila Aspartic Protease Amuc_1434* Inhibits Human Colorectal Cancer LS174T Cell Viability via TRAIL-Mediated Apoptosis Pathway.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Apoptosis/*drug effects ; Aspartic Acid Proteases/*pharmacology ; Bacterial Proteins/*pharmacology ; Recombinant Proteins/*pharmacology ; TNF-Related Apoptosis-Inducing Ligand/*metabolism; Akkermansia/genetics ; Akkermansia/metabolism ; Aspartic Acid Proteases/genetics ; Bacterial Proteins/genetics ; Cell Line, Tumor ; Cell Survival/drug effects ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; G1 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Resting Phase, Cell Cycle/drug effects ; Signal Transduction/drug effects ; Up-Regulation/drug effects
    • Abstract:
      Mucin2 (Muc2) is the main component of the intestinal mucosal layer and is highly expressed in mucous colorectal cancer. Previous studies conducted by our lab found that the recombinant protein Amuc_1434 (expressed in Escherichia coli prokaryote cell system, hereinafter termed Amuc_1434*), derived from Akkermansia muciniphila , can degrade Muc2. Thus, the main objective of this study was to explore the effects of Amuc_1434* on LS174T in colorectal cancer cells expressing Muc2. Results from this study demonstrated that Amuc_1434* inhibited the proliferation of LS174T cells, which was related to its ability to degrade Muc2. Amuc_1434* also blocked the G0/G1 phase of the cell cycle of LS174T cells and upregulated the expression of tumor protein 53 (p53), which is a cell cycle-related protein. In addition, Amuc_1434* promoted apoptosis of LS174T cells and increased mitochondrial ROS levels in LS174T cells. The mitochondrial membrane potential of LS174T cells was also downregulated by Amuc_1434*. Amuc_1434* can activate the death receptor pathway and mitochondrial pathway of apoptosis by upregulating tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL). In conclusion, our study was the first to demonstrate that the protein Amuc_1434* derived from Akkermansia muciniphila suppresses LS174T cell viability via TRAIL-mediated apoptosis pathway.
    • References:
      World J Gastroenterol. 2015 Jan 7;21(1):84-93. (PMID: 25574081)
      J Exp Med. 1998 Dec 21;188(12):2375-80. (PMID: 9858524)
      Cancer Res. 2000 Aug 15;60(16):4315-9. (PMID: 10969767)
      Mitochondrion. 2014 Nov;19 Pt A:39-48. (PMID: 24954615)
      Gastroenterol Rep (Oxf). 2019 Feb;7(1):3-12. (PMID: 30792861)
      J Med Life. 2017 Apr-Jun;10(2):139-143. (PMID: 28616090)
      Carbohydr Res. 2015 Oct 13;415:60-5. (PMID: 26340137)
      BMC Microbiol. 2009 May 27;9:107. (PMID: 19473524)
      J Biol Chem. 2013 Nov 15;288(46):33263-71. (PMID: 24100030)
      Front Microbiol. 2019 May 22;10:1137. (PMID: 31178843)
      Clin Cancer Res. 2001 Jun;7(6):1688-97. (PMID: 11410508)
      Radiat Oncol. 2009 Oct 27;4:49. (PMID: 19860913)
      Oncogene. 2010 Jun 17;29(24):3453-64. (PMID: 20418918)
      Cancer Invest. 2011 Oct;29(8):511-20. (PMID: 21877938)
      Nat Med. 2017 Jan;23(1):107-113. (PMID: 27892954)
      Cancer Epidemiol. 2017 Jun;48:92-95. (PMID: 28437692)
      Biomed Khim. 2017 Jul;63(4):296-305. (PMID: 28862599)
      J Clin Oncol. 1999 Sep;17(9):2941-53. (PMID: 10561374)
      Clin Cancer Res. 2013 Apr 15;19(8):1949-59. (PMID: 23468057)
      PLoS One. 2019 Apr 4;14(4):e0214847. (PMID: 30947287)
      Oncogene. 2001 Jan 18;20(3):399-403. (PMID: 11313970)
      J Biol Chem. 2016 May 27;291(22):11843-51. (PMID: 27053107)
      J Cell Physiol. 2002 Jul;192(1):1-15. (PMID: 12115731)
      Cancer Res. 1999 Nov 15;59(22):5683-6. (PMID: 10582684)
      Cancer Biomark. 2010;9(1-6):235-65. (PMID: 22112479)
      J Clin Invest. 1999 Jul;104(2):155-62. (PMID: 10411544)
      Appl Environ Microbiol. 2015 Jun;81(11):3655-62. (PMID: 25795669)
      Expert Opin Drug Discov. 2013 Sep;8(9):1153-64. (PMID: 23768167)
      Pathol Int. 2007 Aug;57(8):537-47. (PMID: 17610480)
      Cancer Res. 1991 Aug 15;51(16):4436-42. (PMID: 1868464)
      Int J Mol Sci. 2012;13(7):7886-901. (PMID: 22942679)
      Nat Med. 1999 Feb;5(2):157-63. (PMID: 9930862)
      BMC Microbiol. 2006 Mar 08;6:26. (PMID: 16524480)
      Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):77-99. (PMID: 15000151)
      Nat Rev Cancer. 2004 Jan;4(1):45-60. (PMID: 14681689)
      Int J Oncol. 2003 Jan;22(1):15-20. (PMID: 12469180)
      Physiol Rev. 2014 Jul;94(3):909-50. (PMID: 24987008)
      Oncotarget. 2016 Sep 20;7(38):61390-61402. (PMID: 27542217)
      Int J Mol Sci. 2019 Dec 20;21(1):. (PMID: 31861919)
      Cancer Lett. 2009 Nov 18;285(1):1-5. (PMID: 19299078)
      Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):337-48. (PMID: 12787570)
      J Clin Gastroenterol. 2019 Jul;53(6):434-440. (PMID: 29782466)
      Antioxid Redox Signal. 2012 Jun 1;16(11):1295-322. (PMID: 22117137)
      Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Nov;9(6):519-22. (PMID: 17143800)
      Cell. 2009 May 15;137(4):721-35. (PMID: 19427028)
      Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2181-90. (PMID: 21949114)
      PLoS One. 2011 Mar 03;6(3):e16876. (PMID: 21390229)
      J Physiol Pharmacol. 2009 Dec;60 Suppl 6:61-71. (PMID: 20224153)
      Cell Physiol Biochem. 2017;44(2):532-553. (PMID: 29145191)
      Med Sci Monit. 2017 Apr 29;23:2059-2064. (PMID: 28455995)
      Microb Biotechnol. 2019 Nov;12(6):1109-1125. (PMID: 31006995)
      Immunol Rev. 2017 May;277(1):76-89. (PMID: 28462525)
      Anticancer Agents Med Chem. 2018;18(12):1650-1655. (PMID: 29308747)
      Am J Gastroenterol. 2010 Nov;105(11):2420-8. (PMID: 20648002)
      Nat Genet. 1997 Oct;17(2):141-3. (PMID: 9326928)
      J Biol Chem. 2002 Dec 13;277(50):48270-5. (PMID: 12374798)
      Cytotechnology. 2016 Aug;68(4):531-63. (PMID: 26239338)
      Immunity. 1995 Dec;3(6):673-82. (PMID: 8777713)
      Anticancer Res. 2016 Jun;36(6):3224-5. (PMID: 27272863)
      Clin Cancer Res. 2000 Oct;6(10):4017-25. (PMID: 11051251)
      Cancer Lett. 2012 Jan 1;314(1):8-23. (PMID: 22030255)
      J Periodontal Res. 2010 Oct;45(5):650-7. (PMID: 20572922)
      Cold Spring Harb Perspect Biol. 2015 Dec 01;7(12):. (PMID: 26626938)
    • Contributed Indexing:
      Keywords: Amuc_1434*; TRAIL; apoptosis; colorectal cancer cells; proliferation
    • Accession Number:
      0 (Bacterial Proteins)
      0 (Recombinant Proteins)
      0 (TNF-Related Apoptosis-Inducing Ligand)
      EC 3.4.- (Aspartic Acid Proteases)
    • Publication Date:
      Date Created: 20200515 Date Completed: 20210222 Latest Revision: 20210222
    • Publication Date:
      20221213
    • Accession Number:
      PMC7246985
    • Accession Number:
      10.3390/ijms21093385
    • Accession Number:
      32403433