The Effect of Tau and Taxol on Polymerization of MCF7 Microtubules In Vitro.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Feizabadi MS;Feizabadi MS; Castillon VJ; Castillon VJ
  • Source:
    International journal of molecular sciences [Int J Mol Sci] 2022 Jan 08; Vol. 23 (2). Date of Electronic Publication: 2022 Jan 08.
  • Publication Type:
    Journal Article
  • Language:
    English
  • 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:
      Polymerization*; Microtubules/*metabolism ; Paclitaxel/*pharmacology ; tau Proteins/*metabolism; Humans ; MCF-7 Cells ; Microtubules/drug effects
    • Abstract:
      Overexpression of Tau protein in breast cancer cells is identified as an indicator for potential resistance to taxane-based therapy. As reported findings have been obtained mostly from clinical studies, the undetermined underlying mechanism of such drug resistance needs to be thoroughly explored through comprehensive in vitro evaluations. Tau and Taxol bind to the beta tubulin site in microtubules' structure. This is of particular interest in breast cancer, as microtubules of these cancer cells are structurally distinct from some other microtubules, such as neuronal microtubules, due to their unique beta tubulin isotype distribution. The observed changes in the in vitro polymerization of breast cancer microtubules, and the different function of some molecular motors along them, leave open the possibility that the drug resistance mechanism can potentially be associated with different responses of these microtubules to Tau and Taxol. We carried out a series of parallel experiments to allow comparison of the in vitro dual effect of Tau and Taxol on the polymerization of MCF7 microtubules. We observed a concentration-dependent demotion-like alteration in the self-polymerization kinetics of Tau-induced MCF7 microtubules. In contrast, microtubules polymerized under the simultaneous effects of Tau and Taxol showed promoted assembly as compared with those observed in Tau-induced microtubules. The analysis of our data obtained from the length of MCF7 microtubules polymerized under the interaction with Tau and Taxol in vitro suggests that the phenomenon known as drug resistance in microtubule-targeted drugs such as Taxol may not be directly linked to the different responses of microtubules to the drug. The effect of the drug may be mitigated due to the simultaneous interactions with other microtubule-associated proteins such as Tau protein. The observed regulatory effect of Tau and Taxol on the polymerization of breast cancer microtubules in vitro points to additional evidence for the possible role of tubulin isotypes in microtubules' functions.
    • References:
      Sci Rep. 2019 Jul 25;9(1):10795. (PMID: 31346240)
      J Cell Biol. 1981 Nov;91(2 Pt 1):479-87. (PMID: 6118377)
      Traffic. 2015 Oct;16(10):1075-87. (PMID: 26094820)
      Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6746-51. (PMID: 15096589)
      Biochem J. 1992 Sep 1;286 ( Pt 2):399-404. (PMID: 1530572)
      Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11294-11299. (PMID: 27651486)
      Biochemistry. 2009 Oct 27;48(42):10047-55. (PMID: 19769346)
      J Clin Invest. 1997 Sep 1;100(5):1282-93. (PMID: 9276747)
      Cancers (Basel). 2018 Aug 18;10(8):. (PMID: 30126203)
      J Biol Chem. 2002 Nov 8;277(45):42456-62. (PMID: 12207023)
      EMBO J. 1990 Nov;9(11):3539-44. (PMID: 2120043)
      Int J Mol Sci. 2014 Mar 18;15(3):4671-713. (PMID: 24646911)
      J Mol Biol. 1977 Nov 25;117(1):33-52. (PMID: 599568)
      Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8315-20. (PMID: 15914550)
      Biochem Biophys Rep. 2019 Jan 09;17:151-156. (PMID: 30671547)
      Anticancer Res. 2015 Oct;35(10):5179-84. (PMID: 26408675)
      Mol Biol Cell. 1992 Oct;3(10):1141-54. (PMID: 1421571)
      EMBO J. 2003 Jan 2;22(1):70-7. (PMID: 12505985)
      Biochem Biophys Res Commun. 2017 Mar 4;484(2):354-357. (PMID: 28131842)
      Biochem Biophys Res Commun. 2014 Nov 28;454(4):543-6. (PMID: 25450690)
      Cell. 1999 Jan 8;96(1):79-88. (PMID: 9989499)
      Biochem Biophys Res Commun. 2016 Sep 30;478(4):1630-3. (PMID: 27590585)
      Cell Biochem Biophys. 2016 Sep;74(3):373-80. (PMID: 27503105)
      Semin Cell Dev Biol. 2015 Jan;37:11-9. (PMID: 25307498)
      Methods Cell Biol. 2010;95:47-58. (PMID: 20466129)
      Cancer Inform. 2007 Apr 27;3:159-81. (PMID: 19455242)
      Curr Biol. 1995 Aug 1;5(8):900-8. (PMID: 7583148)
      BMC Cancer. 2019 Mar 1;19(1):193. (PMID: 30823906)
      Nature. 1979 Feb 22;277(5698):665-7. (PMID: 423966)
      Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62. (PMID: 1057175)
      J Biol Chem. 1999 Dec 31;274(53):37990-4. (PMID: 10608867)
      Mol Cancer Ther. 2014 Jan;13(1):260-9. (PMID: 24252851)
      J Cell Biol. 1988 Oct;107(4):1437-48. (PMID: 3170635)
      Front Aging Neurosci. 2019 Aug 07;11:204. (PMID: 31447664)
      Biophys J. 2010 Oct 20;99(8):2387-97. (PMID: 20959078)
      Cancer Chemother Pharmacol. 2011 Sep;68(3):553-7. (PMID: 21713447)
      Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9548-53. (PMID: 12886013)
      Front Neurol. 2021 Jan 07;11:595532. (PMID: 33488497)
      Nat Cell Biol. 2014 Apr;16(4):335-44. (PMID: 24633327)
    • Contributed Indexing:
      Keywords: MCF7 cell; Tau protein; Taxol; drug resistance; microtubule; tubulin isotypes
    • Accession Number:
      0 (tau Proteins)
      P88XT4IS4D (Paclitaxel)
    • Publication Date:
      Date Created: 20220121 Date Completed: 20220222 Latest Revision: 20220222
    • Publication Date:
      20231215
    • Accession Number:
      PMC8776089
    • Accession Number:
      10.3390/ijms23020677
    • Accession Number:
      35054875