Display options
Cite
Geletu M, Taha Z, Gunning PT, et al. PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication. Cancers (Basel). 2019;11(2)doi: 10.3390/cancers11020167.
Geletu, M., Taha, Z., Gunning, P. T., & Raptis, L. (2019). PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication. Cancers, 11(2), . https://doi.org/10.3390/cancers11020167
Geletu, Mulu, et al. "PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication." Cancers vol. 11,2 (2019). doi: https://doi.org/10.3390/cancers11020167
Geletu M, Taha Z, Gunning PT, Raptis L. PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication. Cancers (Basel). 2019 Feb 01;11(2). doi: 10.3390/cancers11020167. PMID: 30717267; PMCID: PMC6406562.
Copy Download .nbib Format: NLM
Share it on

Cancers (Basel). 2019 Feb 01;11(2). doi: 10.3390/cancers11020167.

PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication.

Cancers

Mulu Geletu, Zaid Taha, Patrick T Gunning, Leda Raptis

Affiliations

  1. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].
  2. Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].
  3. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].
  4. Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].
  5. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].
  6. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].
  7. Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON K7L 3N6, Canada. [email protected].

PMID: 30717267 PMCID: PMC6406562 DOI: 10.3390/cancers11020167

Abstract

Gap junctional, intercellular communication (GJIC) is interrupted in cells transformed by oncogenes such as activated Src. The Src effector, Ras, is required for this effect, so that Ras inhibition restores GJIC in Src-transformed cells. Interestingly, the inhibition of the Src effector phosphatidyl-inositol-3 kinase (PI3k) or Signal Transducer and Activator of Transcription-3 (Stat3) pathways does not restore GJIC. In the contrary, inhibition of PI3k or Stat3 in non-transformed rodent fibroblasts or epithelial cells or certain human lung carcinoma lines with extensive GJIC inhibits communication, while mutational activation of PI3k or Stat3 increases GJIC. Therefore, it appears that oncogenes such as activated Src have a dual role upon GJIC; acting as inhibitors of communication through the Ras pathway, and as activators through activation of PI3k or Stat3. In the presence of high Src activity the inhibitory functions prevail so that the net effect is gap junction closure. PI3k and Stat3 constitute potent survival signals, so that their inhibition in non-transformed cells triggers apoptosis which, in turn, has been independently demonstrated to suppress GJIC. The interruption of gap junctional communication would confine the apoptotic event to single cells and this might be essential for the maintenance of tissue integrity. We hypothesize that the GJIC activation by PI3k or Stat3 may be linked to their survival function.

Keywords: Src; Stat3; electroporation in situ; gap junctions; phosphatidyl-inositol-3 kinase; polyoma virus middle Tumor antigen

References

  1. J Cell Biol. 1999 Mar 8;144(5):1033-45 - PubMed
  2. Lung Cancer. 1999 Mar;23(3):223-31 - PubMed
  3. Cell. 1999 Aug 6;98(3):295-303 - PubMed
  4. Mol Cell Biol. 1999 Nov;19(11):7519-28 - PubMed
  5. Biochem Biophys Res Commun. 2000 Jun 16;272(3):822-9 - PubMed
  6. J Cell Biol. 2000 Jun 26;149(7):1503-12 - PubMed
  7. J Biol Chem. 2001 Sep 7;276(36):33305-8 - PubMed
  8. J Cell Biol. 2001 Aug 20;154(4):815-27 - PubMed
  9. Exp Cell Res. 2001 Dec 10;271(2):238-48 - PubMed
  10. J Biol Chem. 2002 Feb 22;277(8):6708-18 - PubMed
  11. J Biol Chem. 2002 Mar 8;277(10):8312-20 - PubMed
  12. Oncogene. 2001 Nov 26;20(54):7908-16 - PubMed
  13. J Biol Chem. 2002 Apr 5;277(14):11617-20 - PubMed
  14. Mol Cell Biochem. 2002 Sep;238(1-2):57-68 - PubMed
  15. Dev Cell. 2002 Nov;3(5):631-43 - PubMed
  16. Nat Rev Cancer. 2002 Dec;2(12):951-6 - PubMed
  17. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9434-9 - PubMed
  18. J Biol Chem. 2003 Nov 7;278(45):44852-6 - PubMed
  19. J Virol. 1992 Oct;66(10):5770-6 - PubMed
  20. J Virol. 1992 Sep;66(9):5485-91 - PubMed
  21. Cell Growth Differ. 1992 Sep;3(9):589-96 - PubMed
  22. Oncogene. 2003 Oct 16;22(46):7209-17 - PubMed
  23. Nat Rev Cancer. 2004 Feb;4(2):97-105 - PubMed
  24. J Biol Chem. 2004 May 7;279(19):20058-66 - PubMed
  25. Oncogene. 2004 Apr 8;23(15):2600-16 - PubMed
  26. Biochim Biophys Acta. 2004 Mar 23;1662(1-2):81-95 - PubMed
  27. Int J Biochem Cell Biol. 2004 Jul;36(7):1171-86 - PubMed
  28. J Biol Chem. 2004 Aug 27;279(35):36931-42 - PubMed
  29. J Biol Chem. 2004 Aug 27;279(35):36943-50 - PubMed
  30. Mol Cancer Ther. 2004 Dec;3(12):1533-42 - PubMed
  31. Mol Biol Cell. 2005 Aug;16(8):3832-46 - PubMed
  32. Mol Cell Biol. 2005 Sep;25(17):7432-40 - PubMed
  33. Cell Signal. 2006 May;18(5):592-600 - PubMed
  34. Oncogene. 2006 Apr 13;25(16):2420-4 - PubMed
  35. Cancer Lett. 2006 Oct 8;242(1):120-32 - PubMed
  36. Clin Cancer Res. 2006 Jan 1;12(1):11-9 - PubMed
  37. Mol Cell Biol. 1990 Apr;10(4):1754-63 - PubMed
  38. Cell Commun Adhes. 2006 Jul-Aug;13(4):199-216 - PubMed
  39. Exp Cell Res. 2007 Jan 1;313(1):38-52 - PubMed
  40. J Biol Chem. 2007 Mar 30;282(13):9883-94 - PubMed
  41. Mol Biol Cell. 2007 May;18(5):1734-43 - PubMed
  42. Nat Rev Cancer. 2007 Apr;7(4):281-94 - PubMed
  43. J Virol. 2007 Jul;81(13):7069-76 - PubMed
  44. Cell. 2007 Jun 29;129(7):1261-74 - PubMed
  45. Exp Cell Res. 2007 Dec 10;313(20):4083-90 - PubMed
  46. Exp Cell Res. 2008 Jan 15;314(2):377-86 - PubMed
  47. Mol Cancer Res. 2007 Dec;5(12):1331-41 - PubMed
  48. J Mammary Gland Biol Neoplasia. 2008 Sep;13(3):323-35 - PubMed
  49. Antioxid Redox Signal. 2009 Feb;11(2):323-38 - PubMed
  50. Science. 2009 Feb 6;323(5915):793-7 - PubMed
  51. Biochem Biophys Res Commun. 2009 May 1;382(2):440-4 - PubMed
  52. DNA Cell Biol. 2009 Jul;28(7):319-27 - PubMed
  53. Science. 2009 Jun 26;324(5935):1713-6 - PubMed
  54. Cell Regul. 1990 Dec;1(13):989-1002 - PubMed
  55. Mol Cancer Res. 2009 Aug;7(8):1310-27 - PubMed
  56. Mol Cell Biol. 2010 Jan;30(1):206-19 - PubMed
  57. Nat Rev Cancer. 2009 Nov;9(11):798-809 - PubMed
  58. Exp Cell Res. 2010 Mar 10;316(5):875-86 - PubMed
  59. Biochem Cell Biol. 2009 Dec;87(6):835-43 - PubMed
  60. Biochem Biophys Res Commun. 2010 Sep 17;400(2):230-5 - PubMed
  61. Mol Biol Cell. 2010 Dec;21(23):4089-107 - PubMed
  62. Cell Cycle. 2011 Oct 1;10(19):3221-2 - PubMed
  63. J Biol Chem. 2012 Jan 20;287(4):2600-7 - PubMed
  64. Arch Biochem Biophys. 2012 Aug 1;524(1):16-22 - PubMed
  65. Mol Cell. 2012 Mar 9;45(5):598-609 - PubMed
  66. J Membr Biol. 2012 Jul;245(7):389-400 - PubMed
  67. J Membr Biol. 2012 Aug;245(8):495-506 - PubMed
  68. Anticancer Res. 2012 Oct;32(10):4245-50 - PubMed
  69. BMC Cancer. 2012 Dec 18;12:605 - PubMed
  70. Biochim Biophys Acta. 2013 Aug;1833(8):1947-59 - PubMed
  71. Compr Physiol. 2012 Jul;2(3):1981-2035 - PubMed
  72. Anticancer Res. 2013 Oct;33(10):4401-10 - PubMed
  73. Front Pharmacol. 2013 Oct 22;4:130 - PubMed
  74. J Virol. 1986 Jul;59(1):82-9 - PubMed
  75. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3624-8 - PubMed
  76. Mol Cell Biol. 1987 Feb;7(2):946-50 - PubMed
  77. Cell. 1987 Sep 25;50(7):1021-9 - PubMed
  78. Cell. 1987 Sep 25;50(7):1031-7 - PubMed
  79. FEBS Lett. 2014 Apr 17;588(8):1212-20 - PubMed
  80. Cancer Res. 2014 Feb 1;74(3):641-6 - PubMed
  81. JAKSTAT. 2013 Oct 1;2(4):e27363 - PubMed
  82. FEBS Lett. 2014 Apr 17;588(8):1423-9 - PubMed
  83. J Vis Exp. 2014 Oct 18;(92):e51710 - PubMed
  84. Cell. 1989 Oct 6;59(1):55-65 - PubMed
  85. FEBS Lett. 2015 May 22;589(12):1340-5 - PubMed
  86. Exp Cell Res. 2015 Aug 15;336(2):223-31 - PubMed
  87. Int J Cancer. 2016 Jun 1;138(11):2570-8 - PubMed
  88. Oncol Lett. 2016 Jun;11(6):4134-4138 - PubMed
  89. Nature. 1988 Apr 14;332(6165):644-6 - PubMed
  90. Am J Transl Res. 2017 Dec 15;9(12):5442-5451 - PubMed
  91. Nature. 1985 May 16-22;315(6016):239-42 - PubMed
  92. Medchemcomm. 2016 Oct 14;8(1):96-102 - PubMed
  93. Am J Physiol. 1988 Nov;255(5 Pt 1):C674-83 - PubMed
  94. Nature. 1966 Mar 19;209(5029):1248-9 - PubMed
  95. J Virol. 1981 Jun;38(3):958-67 - PubMed
  96. Nature. 1994 Jan 6;367(6458):87-90 - PubMed
  97. Cell. 1993 Mar 12;72(5):767-78 - PubMed
  98. DNA Cell Biol. 1994 Sep;13(9):963-75 - PubMed
  99. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6344-8 - PubMed
  100. Cancer Lett. 1996 May 15;103(1):99-106 - PubMed
  101. DNA Cell Biol. 1996 Jun;15(6):443-51 - PubMed
  102. Cell Growth Differ. 1996 Jun;7(6):737-43 - PubMed
  103. Cell. 1997 Feb 21;88(4):435-7 - PubMed
  104. Cancer Detect Prev. 1997;21(4):289-94 - PubMed
  105. Cell. 1997 Oct 17;91(2):231-41 - PubMed
  106. Nature. 1997 Nov 13;390(6656):116-7 - PubMed
  107. Mol Cell Biol. 1998 Apr;18(4):2344-59 - PubMed
  108. Mol Cell Biol. 1998 May;18(5):2545-52 - PubMed
  109. Mol Cell Biol. 1998 May;18(5):2553-8 - PubMed
  110. Circ Res. 1998 Sep 21;83(6):629-35 - PubMed
  111. Cancer Res. 1998 Nov 15;58(22):5089-96 - PubMed

Publication Types