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SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3

Suppressor of cytokine signaling 3 (SOCS3) is a major negative regulator of signal transducer and activator of transcription 3 (STAT3) during tumorigenesis. Previous studies have indicated that SOCS3 also regulates other signaling pathways, such as PI3K/Akt. However, little is known about the specif...

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Autores principales: WAN, JUN, CHE, YUN, KANG, NINGNING, WU, WEI
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438922/
https://www.ncbi.nlm.nih.gov/pubmed/25695729
http://dx.doi.org/10.3892/mmr.2015.3368
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author WAN, JUN
CHE, YUN
KANG, NINGNING
WU, WEI
author_facet WAN, JUN
CHE, YUN
KANG, NINGNING
WU, WEI
author_sort WAN, JUN
collection PubMed
description Suppressor of cytokine signaling 3 (SOCS3) is a major negative regulator of signal transducer and activator of transcription 3 (STAT3) during tumorigenesis. Previous studies have indicated that SOCS3 also regulates other signaling pathways, such as PI3K/Akt. However, little is known about the specific molecular mechanisms by which SOCS3 regulates the proliferation and angiogenesis of small cell lung cancer (SCLC) cells. The present study investigated the effect of SOCS3 upregulation on the expression of hypoxia-inducible factor-1α (HIF-1α) and how this affects the proliferation and angiogenesis of SCLC cells. It was investigated whether this interaction is associated with STAT3 or the Akt signaling pathway. The results of the present study revealed that SOCS3 negatively regulates proliferation and angiogenesis of NCI-H446 cells and that HIF-1α is required in this process. The results also suggested a suppressive role of SOCS3 in Akt signaling, but not STAT3 signaling to block HIF-1α expression and a previously unidentified regulatory mechanism for Akt function. In conclusion, the present study suggested that SOCS3 targets the Akt signaling pathway to inhibit HIF-1α expression and affect the growth and angio-genesis of SCLC cells, and may therefore be considered as a potential novel therapeutic for the treatment of SCLC.
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spelling pubmed-44389222015-06-05 SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3 WAN, JUN CHE, YUN KANG, NINGNING WU, WEI Mol Med Rep Articles Suppressor of cytokine signaling 3 (SOCS3) is a major negative regulator of signal transducer and activator of transcription 3 (STAT3) during tumorigenesis. Previous studies have indicated that SOCS3 also regulates other signaling pathways, such as PI3K/Akt. However, little is known about the specific molecular mechanisms by which SOCS3 regulates the proliferation and angiogenesis of small cell lung cancer (SCLC) cells. The present study investigated the effect of SOCS3 upregulation on the expression of hypoxia-inducible factor-1α (HIF-1α) and how this affects the proliferation and angiogenesis of SCLC cells. It was investigated whether this interaction is associated with STAT3 or the Akt signaling pathway. The results of the present study revealed that SOCS3 negatively regulates proliferation and angiogenesis of NCI-H446 cells and that HIF-1α is required in this process. The results also suggested a suppressive role of SOCS3 in Akt signaling, but not STAT3 signaling to block HIF-1α expression and a previously unidentified regulatory mechanism for Akt function. In conclusion, the present study suggested that SOCS3 targets the Akt signaling pathway to inhibit HIF-1α expression and affect the growth and angio-genesis of SCLC cells, and may therefore be considered as a potential novel therapeutic for the treatment of SCLC. D.A. Spandidos 2015-07 2015-02-17 /pmc/articles/PMC4438922/ /pubmed/25695729 http://dx.doi.org/10.3892/mmr.2015.3368 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
WAN, JUN
CHE, YUN
KANG, NINGNING
WU, WEI
SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3
title SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3
title_full SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3
title_fullStr SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3
title_full_unstemmed SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3
title_short SOCS3 blocks HIF-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of Akt, but not STAT3
title_sort socs3 blocks hif-1α expression to inhibit proliferation and angiogenesis of human small cell lung cancer by downregulating activation of akt, but not stat3
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438922/
https://www.ncbi.nlm.nih.gov/pubmed/25695729
http://dx.doi.org/10.3892/mmr.2015.3368
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