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

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...

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Autores principales: Geletu, Mulu, Taha, Zaid, Gunning, Patrick T., Raptis, Leda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406562/
https://www.ncbi.nlm.nih.gov/pubmed/30717267
http://dx.doi.org/10.3390/cancers11020167
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author Geletu, Mulu
Taha, Zaid
Gunning, Patrick T.
Raptis, Leda
author_facet Geletu, Mulu
Taha, Zaid
Gunning, Patrick T.
Raptis, Leda
author_sort Geletu, Mulu
collection PubMed
description 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.
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spelling pubmed-64065622019-03-21 PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication Geletu, Mulu Taha, Zaid Gunning, Patrick T. Raptis, Leda Cancers (Basel) Review 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. MDPI 2019-02-01 /pmc/articles/PMC6406562/ /pubmed/30717267 http://dx.doi.org/10.3390/cancers11020167 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Geletu, Mulu
Taha, Zaid
Gunning, Patrick T.
Raptis, Leda
PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
title PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
title_full PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
title_fullStr PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
title_full_unstemmed PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
title_short PI3k and Stat3: Oncogenes that are Required for Gap Junctional, Intercellular Communication
title_sort pi3k and stat3: oncogenes that are required for gap junctional, intercellular communication
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406562/
https://www.ncbi.nlm.nih.gov/pubmed/30717267
http://dx.doi.org/10.3390/cancers11020167
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