Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin.
The insulin-like growth factor (IGF) type 1 receptor is required for growth, transformation, and protection from apoptosis. IGFs can enhance cell migration, which is known to be influenced via regulation of the E-cadherin/beta-catenin complex. We sought to investigate whether IGF-1 modulated the int...
| Main Authors: | , , , |
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| Format: | Journal article |
| Sprog: | English |
| Udgivet: |
2000
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| _version_ | 1826298391323213824 |
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| author | Playford, M Bicknell, D Bodmer, W Macaulay, V |
| author_facet | Playford, M Bicknell, D Bodmer, W Macaulay, V |
| author_sort | Playford, M |
| collection | OXFORD |
| description | The insulin-like growth factor (IGF) type 1 receptor is required for growth, transformation, and protection from apoptosis. IGFs can enhance cell migration, which is known to be influenced via regulation of the E-cadherin/beta-catenin complex. We sought to investigate whether IGF-1 modulated the interaction between E-cadherin and beta-catenin in human colorectal cancer cells. We used the C10 cell line, which we established and have previously shown to lack adenomatous polyposis coli, E-cadherin, or beta-catenin mutations. We found that IGF-1 stimulation enhanced tyrosine phosphorylation of two proteins, beta-catenin and insulin-receptor substrate 1, which formed a complex with E-cadherin. Tyrosine phosphorylation of beta-catenin was accompanied by rapid (<1 min) dissociation from E-cadherin at the plasma membrane, followed by relocation to the cellular cytoplasm. IGF-1 also enhanced the stability of beta-catenin protein. Despite this, we observed no enhancement of transcriptional activity in complex with T-cell factor 4 (Tcf-4) in human embryonic kidney 293 cells treated with IGF-1 or insulin alone. IGF-1 did, however, enhance transcriptional activity in combination with lithium chloride, an inhibitor of glycogen synthase kinase 3 beta, which also stabilizes beta-catenin. In conclusion, we have shown that IGF-1 causes tyrosine phosphorylation and stabilization of beta-catenin. These effects may contribute to transformation, cell migration, and a propensity for metastasis in vivo. |
| first_indexed | 2024-03-07T04:46:07Z |
| format | Journal article |
| id | oxford-uuid:d3567818-bf9c-42b4-b547-becc1e055ec1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:46:07Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:d3567818-bf9c-42b4-b547-becc1e055ec12022-03-27T08:10:31ZInsulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d3567818-bf9c-42b4-b547-becc1e055ec1EnglishSymplectic Elements at Oxford2000Playford, MBicknell, DBodmer, WMacaulay, VThe insulin-like growth factor (IGF) type 1 receptor is required for growth, transformation, and protection from apoptosis. IGFs can enhance cell migration, which is known to be influenced via regulation of the E-cadherin/beta-catenin complex. We sought to investigate whether IGF-1 modulated the interaction between E-cadherin and beta-catenin in human colorectal cancer cells. We used the C10 cell line, which we established and have previously shown to lack adenomatous polyposis coli, E-cadherin, or beta-catenin mutations. We found that IGF-1 stimulation enhanced tyrosine phosphorylation of two proteins, beta-catenin and insulin-receptor substrate 1, which formed a complex with E-cadherin. Tyrosine phosphorylation of beta-catenin was accompanied by rapid (<1 min) dissociation from E-cadherin at the plasma membrane, followed by relocation to the cellular cytoplasm. IGF-1 also enhanced the stability of beta-catenin protein. Despite this, we observed no enhancement of transcriptional activity in complex with T-cell factor 4 (Tcf-4) in human embryonic kidney 293 cells treated with IGF-1 or insulin alone. IGF-1 did, however, enhance transcriptional activity in combination with lithium chloride, an inhibitor of glycogen synthase kinase 3 beta, which also stabilizes beta-catenin. In conclusion, we have shown that IGF-1 causes tyrosine phosphorylation and stabilization of beta-catenin. These effects may contribute to transformation, cell migration, and a propensity for metastasis in vivo. |
| spellingShingle | Playford, M Bicknell, D Bodmer, W Macaulay, V Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
| title | Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
| title_full | Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
| title_fullStr | Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
| title_full_unstemmed | Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
| title_short | Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
| title_sort | insulin like growth factor 1 regulates the location stability and transcriptional activity of beta catenin |
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