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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3559342?pdf=render |
| _version_ | 1818246929971150848 |
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| author | Byungtak Kim Seongeun Kang Sun Jung Kim |
| author_facet | Byungtak Kim Seongeun Kang Sun Jung Kim |
| author_sort | Byungtak Kim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T14:56:37Z |
| format | Article |
| id | doaj.art-eb8b5b9a1ad94fbca344b718e7f95a55 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T14:56:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-eb8b5b9a1ad94fbca344b718e7f95a552022-12-22T00:20:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5533810.1371/journal.pone.0055338Genome-wide pathway analysis reveals different signaling pathways between secreted lactoferrin and intracellular delta-lactoferrin.Byungtak KimSeongeun KangSun Jung KimHuman 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.http://europepmc.org/articles/PMC3559342?pdf=render |
| spellingShingle | Byungtak Kim Seongeun Kang Sun Jung Kim Genome-wide pathway analysis reveals different signaling pathways between secreted lactoferrin and intracellular delta-lactoferrin. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3559342?pdf=render |
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