A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation.
Aberrant Wnt signaling has been implicated in a wide variety of cancers and many components of the Wnt signaling network have now been identified. Much less is known, however, about how these proteins are coordinately regulated. Here, a broad, quantitative, and dynamic study of Wnt3a-mediated stimul...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2850918?pdf=render |
| _version_ | 1811216429334134784 |
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| author | Taranjit S Gujral Gavin MacBeath |
| author_facet | Taranjit S Gujral Gavin MacBeath |
| author_sort | Taranjit S Gujral |
| collection | DOAJ |
| description | Aberrant Wnt signaling has been implicated in a wide variety of cancers and many components of the Wnt signaling network have now been identified. Much less is known, however, about how these proteins are coordinately regulated. Here, a broad, quantitative, and dynamic study of Wnt3a-mediated stimulation of HEK 293 cells revealed two phases of transcriptional regulation: an early phase in which signaling antagonists were downregulated, providing positive feedback, and a later phase in which many of these same antagonists were upregulated, attenuating signaling. The dynamic expression profiles of several response genes, including MYC and CTBP1, correlated significantly with proliferation and migration (P<0.05). Additionally, their levels tracked with the tumorigenicity of colon cancer cell lines and they were significantly overexpressed in colorectal adenocarcinomas (P<0.05). Our data highlight CtBP1 as a transcription factor that contributes to positive feedback during the early phases of Wnt signaling and serves as a novel marker for colorectal cancer progression. |
| first_indexed | 2024-04-12T06:39:04Z |
| format | Article |
| id | doaj.art-68b02fd9caaa4922a1efcd06d585f319 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T06:39:04Z |
| publishDate | 2010-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-68b02fd9caaa4922a1efcd06d585f3192022-12-22T03:43:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1002410.1371/journal.pone.0010024A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation.Taranjit S GujralGavin MacBeathAberrant Wnt signaling has been implicated in a wide variety of cancers and many components of the Wnt signaling network have now been identified. Much less is known, however, about how these proteins are coordinately regulated. Here, a broad, quantitative, and dynamic study of Wnt3a-mediated stimulation of HEK 293 cells revealed two phases of transcriptional regulation: an early phase in which signaling antagonists were downregulated, providing positive feedback, and a later phase in which many of these same antagonists were upregulated, attenuating signaling. The dynamic expression profiles of several response genes, including MYC and CTBP1, correlated significantly with proliferation and migration (P<0.05). Additionally, their levels tracked with the tumorigenicity of colon cancer cell lines and they were significantly overexpressed in colorectal adenocarcinomas (P<0.05). Our data highlight CtBP1 as a transcription factor that contributes to positive feedback during the early phases of Wnt signaling and serves as a novel marker for colorectal cancer progression.http://europepmc.org/articles/PMC2850918?pdf=render |
| spellingShingle | Taranjit S Gujral Gavin MacBeath A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. PLoS ONE |
| title | A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. |
| title_full | A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. |
| title_fullStr | A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. |
| title_full_unstemmed | A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. |
| title_short | A system-wide investigation of the dynamics of Wnt signaling reveals novel phases of transcriptional regulation. |
| title_sort | system wide investigation of the dynamics of wnt signaling reveals novel phases of transcriptional regulation |
| url | http://europepmc.org/articles/PMC2850918?pdf=render |
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