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Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin
Human lactoferrin (LF) is a multifunctional protein involved in immunomodulation, cellular growth, and differentiation. In addition to its secreted form (sLF), an alternative form (ΔLF) lacking the signal sequence has been found to be downregulated in cancer. Although the signaling pathways mediated...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559342/ https://www.ncbi.nlm.nih.gov/pubmed/23383159 http://dx.doi.org/10.1371/journal.pone.0055338 |
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author | Kim, Byungtak Kang, Seongeun Kim, Sun Jung |
author_facet | Kim, Byungtak Kang, Seongeun Kim, Sun Jung |
author_sort | Kim, Byungtak |
collection | PubMed |
description | Human lactoferrin (LF) is a multifunctional protein involved in immunomodulation, cellular growth, and differentiation. In addition to its secreted form (sLF), an alternative form (ΔLF) lacking the signal sequence has been found to be downregulated in cancer. Although the signaling pathways mediated by LF have been studied in a few cell models, there have been no relevant systemic approaches. Therefore, this study was carried out to identify and compare signaling networks provoked by the two LF isoforms. For this, the two forms were overexpressed in HEK293 cells using the Flp-In T-Rex system, after which genome-wide expression analysis of 18,367 genes was conducted. Pathway analysis of the genes showing altered expression identified pathways which are responsible for cell survival and apoptosis. In addition, the pathways mediated by the two LF forms were within distantly related networks. GPCR, PI3K complex, and POU5F1, which are involved in receptor-mediated pathways, were centered in the sLF network, whereas RIF1, NOS3, and RNPS1, which are involved in intracellular signaling, were centered in the ΔLF network. These results suggest that structural differences between the LF isoforms, mainly glycosylation, determine the fate of LF signaling. Furthermore, these findings provide information relating to the role of ΔLF which is downregulated during carcinogenesis. |
format | Online Article Text |
id | pubmed-3559342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35593422013-02-04 Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin Kim, Byungtak Kang, Seongeun Kim, Sun Jung PLoS One Research Article Human lactoferrin (LF) is a multifunctional protein involved in immunomodulation, cellular growth, and differentiation. In addition to its secreted form (sLF), an alternative form (ΔLF) lacking the signal sequence has been found to be downregulated in cancer. Although the signaling pathways mediated by LF have been studied in a few cell models, there have been no relevant systemic approaches. Therefore, this study was carried out to identify and compare signaling networks provoked by the two LF isoforms. For this, the two forms were overexpressed in HEK293 cells using the Flp-In T-Rex system, after which genome-wide expression analysis of 18,367 genes was conducted. Pathway analysis of the genes showing altered expression identified pathways which are responsible for cell survival and apoptosis. In addition, the pathways mediated by the two LF forms were within distantly related networks. GPCR, PI3K complex, and POU5F1, which are involved in receptor-mediated pathways, were centered in the sLF network, whereas RIF1, NOS3, and RNPS1, which are involved in intracellular signaling, were centered in the ΔLF network. These results suggest that structural differences between the LF isoforms, mainly glycosylation, determine the fate of LF signaling. Furthermore, these findings provide information relating to the role of ΔLF which is downregulated during carcinogenesis. Public Library of Science 2013-01-30 /pmc/articles/PMC3559342/ /pubmed/23383159 http://dx.doi.org/10.1371/journal.pone.0055338 Text en © 2013 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Byungtak Kang, Seongeun Kim, Sun Jung Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin |
title | Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin |
title_full | Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin |
title_fullStr | Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin |
title_full_unstemmed | Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin |
title_short | Genome-Wide Pathway Analysis Reveals Different Signaling Pathways between Secreted Lactoferrin and Intracellular Delta-Lactoferrin |
title_sort | genome-wide pathway analysis reveals different signaling pathways between secreted lactoferrin and intracellular delta-lactoferrin |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559342/ https://www.ncbi.nlm.nih.gov/pubmed/23383159 http://dx.doi.org/10.1371/journal.pone.0055338 |
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