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FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with th...

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Autores principales: Li, Chien-Hsiu, Chang, Yu-Chan, Hsiao, Michael, Liang, Shu-Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966623/
https://www.ncbi.nlm.nih.gov/pubmed/31795213
http://dx.doi.org/10.3390/cancers11121897
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author Li, Chien-Hsiu
Chang, Yu-Chan
Hsiao, Michael
Liang, Shu-Mei
author_facet Li, Chien-Hsiu
Chang, Yu-Chan
Hsiao, Michael
Liang, Shu-Mei
author_sort Li, Chien-Hsiu
collection PubMed
description Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with the Gal-3 promoter to upregulate Gal-3 in FOXD1-overexpressing CL1-0 lung cancer cells. Ectopic expression of FOXD1 increased the expression of Gal-3 and the growth and motility of lung cancer cells, whereas depletion of Gal-3 attenuated FOXD1-mediated tumorigenesis. ERK1/2 interacted with FOXD1 in the cytosol and translocated FOXD1 into the nucleus to activate Gal-3. Gal-3 in turn upregulated FOXD1 via the transcription factor proto-oncogene 1 (ETS-1) to transactivate FOXD1. The increase in ETS-1/FOXD1 expression by Gal-3 was through Gal-3-mediated integrin-β1 (ITGβ1) signaling. The overexpression of both FOXD1 and Gal-3 form a positive regulatory loop to promote lung cancer aggressiveness. Moreover, both FOXD1 and Gal-3 were positively correlated in human lung cancer tissues. Our findings demonstrated that FOXD1 and Gal-3 form a positive feedback loop in lung cancer, and interference of this loop may serve as an effective therapeutic target for the treatment of lung cancers, particularly those related to dysregulation of Gal-3.
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spelling pubmed-69666232020-02-04 FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness Li, Chien-Hsiu Chang, Yu-Chan Hsiao, Michael Liang, Shu-Mei Cancers (Basel) Article Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with the Gal-3 promoter to upregulate Gal-3 in FOXD1-overexpressing CL1-0 lung cancer cells. Ectopic expression of FOXD1 increased the expression of Gal-3 and the growth and motility of lung cancer cells, whereas depletion of Gal-3 attenuated FOXD1-mediated tumorigenesis. ERK1/2 interacted with FOXD1 in the cytosol and translocated FOXD1 into the nucleus to activate Gal-3. Gal-3 in turn upregulated FOXD1 via the transcription factor proto-oncogene 1 (ETS-1) to transactivate FOXD1. The increase in ETS-1/FOXD1 expression by Gal-3 was through Gal-3-mediated integrin-β1 (ITGβ1) signaling. The overexpression of both FOXD1 and Gal-3 form a positive regulatory loop to promote lung cancer aggressiveness. Moreover, both FOXD1 and Gal-3 were positively correlated in human lung cancer tissues. Our findings demonstrated that FOXD1 and Gal-3 form a positive feedback loop in lung cancer, and interference of this loop may serve as an effective therapeutic target for the treatment of lung cancers, particularly those related to dysregulation of Gal-3. MDPI 2019-11-28 /pmc/articles/PMC6966623/ /pubmed/31795213 http://dx.doi.org/10.3390/cancers11121897 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 Article
Li, Chien-Hsiu
Chang, Yu-Chan
Hsiao, Michael
Liang, Shu-Mei
FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness
title FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness
title_full FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness
title_fullStr FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness
title_full_unstemmed FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness
title_short FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness
title_sort foxd1 and gal-3 form a positive regulatory loop to regulate lung cancer aggressiveness
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966623/
https://www.ncbi.nlm.nih.gov/pubmed/31795213
http://dx.doi.org/10.3390/cancers11121897
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