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Oncotarget. 2017 Sep 11;8(44):76686-76698. doi: 10.18632/oncotarget.20805. eCollection 2017 Sep 29.

Septin remodeling is essential for the formation of cell membrane protrusions (microtentacles) in detached tumor cells.

Oncotarget

Kristine Østevold, Ana V Meléndez, Friederike Lehmann, Gudula Schmidt, Klaus Aktories, Carsten Schwan

Affiliations

  1. Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, 79104 Freiburg, Germany.
  2. Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
  3. Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104 Freiburg, Germany.
  4. Faculty of Chemistry and Pharmacy, University of Freiburg, 79104 Freiburg, Germany.
  5. Centre for Biological Signalling Studies (BIOSS), University of Freiburg, 79104 Freiburg, Germany.

PMID: 29100341 PMCID: PMC5652735 DOI: 10.18632/oncotarget.20805

Abstract

Microtentacles are mostly microtubule-based cell protrusions that are formed by detached tumor cells. Here, we report that the formation of tumor cell microtentacles depends on the presence and dynamics of guanine nucleotide-binding proteins of the septin family, which are part of the cytoskeleton. In matrix-attached breast, lung, prostate and pancreas cancer cells, septins are associated with the cytosolic actin cytoskeleton. Detachment of cells causes redistribution of septins to the membrane, where microtentacle formation occurs. Forchlorfenuron, which inhibits septin functions, blocks microtentacle formation. The small GTPase Cdc42 and its effector proteins Borgs regulate septins and are essential for microtentacle formation. Dominant active and inactive Cdc42 inhibit microtentacle formation indicating that the free cycling of Cdc42 between its active and inactive state is essential for septin regulation and microtentacle formation. Cell attachment and aggregation models suggest that septins play an essential role in the metastatic behavior of tumor cells.

Keywords: Clostridium difficile toxin; actin ADP-ribosylation; microtentacles; microtubules; septin

Conflict of interest statement

CONFLICTS OF INTEREST None.

References

  1. Nat Rev Cancer. 2016 Apr;16(4):201-18 - PubMed
  2. Mol Cancer Res. 2010 May;8(5):643-52 - PubMed
  3. Science. 2004 Jul 2;305(5680):61-6 - PubMed
  4. Cell Rep. 2015 Dec 29;13(12 ):2699-714 - PubMed
  5. Nature. 2013 Jul 11;499(7457):238-42 - PubMed
  6. Pathol Oncol Res. 2011 Sep;17(3):503-9 - PubMed
  7. Nat Rev Mol Cell Biol. 2008 Jun;9(6):478-89 - PubMed
  8. Oncotarget. 2015 Mar 20;6(8):6251-66 - PubMed
  9. J Biol Chem. 2015 Feb 27;290(9):5280-97 - PubMed
  10. J Clin Invest. 2009 Jun;119(6):1420-8 - PubMed
  11. Clin Chem. 2008 Feb;54(2):414-23 - PubMed
  12. Transl Oncol. 2010 Aug 01;3(4):239-45 - PubMed
  13. Mol Biol Cell. 2014 Mar;25(6):841-51 - PubMed
  14. Cancer Res. 2010 Oct 15;70(20):7737-41 - PubMed
  15. Nat Rev Mol Cell Biol. 2012 Feb 08;13(3):183-94 - PubMed
  16. J Biol Chem. 2008 Oct 24;283(43):29563-71 - PubMed
  17. Exp Cell Res. 2004 Sep 10;299(1):236-47 - PubMed
  18. J Biol Chem. 2003 Jan 31;278(5):3483-8 - PubMed
  19. Exp Cell Res. 2007 Apr 15;313(7):1326-36 - PubMed
  20. Breast Cancer Res. 2011 Aug 10;13(4):R76 - PubMed
  21. PLoS Pathog. 2009 Oct;5(10):e1000626 - PubMed
  22. PLoS One. 2008;3(11):e3759 - PubMed
  23. Cancer Res. 1999 Sep 1;59(17):4261-5 - PubMed
  24. J Cell Biol. 2002 Jan 21;156(2):315-26 - PubMed
  25. Neuron. 1998 Jun;20(6):1111-22 - PubMed
  26. Curr Biol. 2012 Jun 19;22(12):1109-15 - PubMed
  27. J Cell Sci. 2013 Jun 15;126(Pt 12):2583-94 - PubMed
  28. Cell. 2014 Aug 28;158(5):1110-1122 - PubMed
  29. Oncotarget. 2016 Sep 20;7(38):61587-61600 - PubMed
  30. Biol Chem. 2013 Feb;394(2):281-90 - PubMed
  31. Dev Cell. 2002 Dec;3(6):791-802 - PubMed
  32. Int Rev Cell Mol Biol. 2014;310:289-339 - PubMed
  33. Nat Cell Biol. 2009 Jan;11(1):17-26 - PubMed
  34. Nat Commun. 2016 May 26;7: - PubMed
  35. Mol Biol Cell. 2011 Sep;22(17):3152-64 - PubMed
  36. Cancer Res. 2010 May 1;70(9):3780-90 - PubMed
  37. Cancer Res. 2006 Jan 15;66(2):856-66 - PubMed
  38. Curr Opin Cell Biol. 2008 Feb;20(1):85-90 - PubMed
  39. J Biol Chem. 2015 Jul 10;290(28):17173-80 - PubMed
  40. Oncogene. 2010 Dec 2;29(48):6402-8 - PubMed
  41. Nat Rev Cancer. 2005 Aug;5(8):591-602 - PubMed
  42. Cancer Res. 2003 May 1;63(9):2179-87 - PubMed
  43. Nat Rev Cancer. 2006 Jun;6(6):449-58 - PubMed
  44. Cancers (Basel). 2013 Nov 14;5(4):1545-65 - PubMed
  45. J Pathol. 2003 Dec;201(4):581-8 - PubMed
  46. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2313-8 - PubMed
  47. Curr Opin Cell Biol. 1996 Feb;8(1):106-19 - PubMed
  48. Clin Cancer Res. 2015 Dec 1;21(23 ):5209-5214 - PubMed
  49. Curr Opin Cell Biol. 2012 Oct;24(5):569-81 - PubMed
  50. Curr Top Microbiol Immunol. 2017;399:35-51 - PubMed
  51. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6428-33 - PubMed
  52. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7870-5 - PubMed
  53. Oncogene. 2013 Apr 25;32(17 ):2200-10 - PubMed
  54. Elife. 2013 Nov 28;2:e01085 - PubMed
  55. Dev Cell. 2003 Mar;4(3):345-57 - PubMed
  56. Cancer Genet Cytogenet. 2007 Jul 1;176(1):72-5 - PubMed
  57. Nat Cell Biol. 2001 Oct;3(10):861-6 - PubMed
  58. Nature. 2007 Sep 20;449(7160):311-5 - PubMed
  59. Clin Exp Metastasis. 2007;24(8):587-97 - PubMed
  60. J Cell Sci. 2010 Dec 15;123(Pt 24):4195-200 - PubMed
  61. J Cell Biol. 1990 Jul;111(1):131-42 - PubMed

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