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Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway

Bmal1 is a core factor in the regulation of circadian rhythms. Previous studies have shown that Bmal1 suppresses tumor growth in cell culture and animal models and is down-regulated in certain types of cancer. The aim of the present study was to investigated whether Bmal1 influences the invasiveness...

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Autores principales: JUNG, CHAN-HUN, KIM, EUN MI, PARK, JONG KUK, HWANG, SANG-GU, MOON, SUNG-KWON, KIM, WUN-JAE, UM, HONG-DUCK
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694561/
https://www.ncbi.nlm.nih.gov/pubmed/23563360
http://dx.doi.org/10.3892/or.2013.2381
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author JUNG, CHAN-HUN
KIM, EUN MI
PARK, JONG KUK
HWANG, SANG-GU
MOON, SUNG-KWON
KIM, WUN-JAE
UM, HONG-DUCK
author_facet JUNG, CHAN-HUN
KIM, EUN MI
PARK, JONG KUK
HWANG, SANG-GU
MOON, SUNG-KWON
KIM, WUN-JAE
UM, HONG-DUCK
author_sort JUNG, CHAN-HUN
collection PubMed
description Bmal1 is a core factor in the regulation of circadian rhythms. Previous studies have shown that Bmal1 suppresses tumor growth in cell culture and animal models and is down-regulated in certain types of cancer. The aim of the present study was to investigated whether Bmal1 influences the invasiveness of cancer cells. We demonstrated that knockdown of Bmal1 by RNA interference promoted cancer cell invasion, whereas its overexpression reduced cellular invasiveness. These effects were observed in lung cancer and glioma cells, and occurred regardless of p53 status. Therefore, it appears that Bmal1 suppresses the invasion of multiple cancer types in a p53-independent manner. Bmal1 knockdown-induced cancer cell invasion was accompanied by activation of the PI3K-Akt-MMP-2 pathway, and was prevented by inhibitors of PI3K, Akt or MMP-2. This suggests that Bmal1 suppresses cell invasion by blocking the PI3K-Akt-MMP-2 pathway. Since this invasion pathway is activated by the oncogene Bcl-w, we investigated whether Bmal1 affects the activity of Bcl-w. As expected, Bmal1 attenuated the ability of Bcl-w to promote MMP-2 accumulation and cell invasion, supporting the idea that Bmal1 antagonizes Bcl-w activity. Collectively, our data suggest that Bmal1 is a tumor suppressor, capable of suppressing cancer cell growth and invasiveness, and support the recent proposal that there is a tight molecular link between circadian rhythms and tumor formation/progression.
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spelling pubmed-36945612013-06-27 Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway JUNG, CHAN-HUN KIM, EUN MI PARK, JONG KUK HWANG, SANG-GU MOON, SUNG-KWON KIM, WUN-JAE UM, HONG-DUCK Oncol Rep Articles Bmal1 is a core factor in the regulation of circadian rhythms. Previous studies have shown that Bmal1 suppresses tumor growth in cell culture and animal models and is down-regulated in certain types of cancer. The aim of the present study was to investigated whether Bmal1 influences the invasiveness of cancer cells. We demonstrated that knockdown of Bmal1 by RNA interference promoted cancer cell invasion, whereas its overexpression reduced cellular invasiveness. These effects were observed in lung cancer and glioma cells, and occurred regardless of p53 status. Therefore, it appears that Bmal1 suppresses the invasion of multiple cancer types in a p53-independent manner. Bmal1 knockdown-induced cancer cell invasion was accompanied by activation of the PI3K-Akt-MMP-2 pathway, and was prevented by inhibitors of PI3K, Akt or MMP-2. This suggests that Bmal1 suppresses cell invasion by blocking the PI3K-Akt-MMP-2 pathway. Since this invasion pathway is activated by the oncogene Bcl-w, we investigated whether Bmal1 affects the activity of Bcl-w. As expected, Bmal1 attenuated the ability of Bcl-w to promote MMP-2 accumulation and cell invasion, supporting the idea that Bmal1 antagonizes Bcl-w activity. Collectively, our data suggest that Bmal1 is a tumor suppressor, capable of suppressing cancer cell growth and invasiveness, and support the recent proposal that there is a tight molecular link between circadian rhythms and tumor formation/progression. D.A. Spandidos 2013-06 2013-04-03 /pmc/articles/PMC3694561/ /pubmed/23563360 http://dx.doi.org/10.3892/or.2013.2381 Text en Copyright © 2013, 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
JUNG, CHAN-HUN
KIM, EUN MI
PARK, JONG KUK
HWANG, SANG-GU
MOON, SUNG-KWON
KIM, WUN-JAE
UM, HONG-DUCK
Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway
title Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway
title_full Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway
title_fullStr Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway
title_full_unstemmed Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway
title_short Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway
title_sort bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-akt-mmp-2 signaling pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694561/
https://www.ncbi.nlm.nih.gov/pubmed/23563360
http://dx.doi.org/10.3892/or.2013.2381
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