Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1
Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchy...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717311828 |
| _version_ | 1811286933084569600 |
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| author | Archis Bagati Anna Bianchi-Smiraglia Sudha Moparthy Kateryna Kolesnikova Emily E. Fink Brittany C. Lipchick Masha Kolesnikova Peter Jowdy Anthony Polechetti Amin Mahpour Jason Ross Joseph A. Wawrzyniak Dong Hyun Yun Gyorgy Paragh Nadezhda I. Kozlova Albert E. Berman Jianmin Wang Song Liu Michael J. Nemeth Mikhail A. Nikiforov |
| author_facet | Archis Bagati Anna Bianchi-Smiraglia Sudha Moparthy Kateryna Kolesnikova Emily E. Fink Brittany C. Lipchick Masha Kolesnikova Peter Jowdy Anthony Polechetti Amin Mahpour Jason Ross Joseph A. Wawrzyniak Dong Hyun Yun Gyorgy Paragh Nadezhda I. Kozlova Albert E. Berman Jianmin Wang Song Liu Michael J. Nemeth Mikhail A. Nikiforov |
| author_sort | Archis Bagati |
| collection | DOAJ |
| description | Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) transcription of the N-cadherin gene (CDH2). We demonstrate that FOXQ1 interacts with nuclear β-catenin and TLE proteins, and the β-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear β-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes. |
| first_indexed | 2024-04-13T03:08:42Z |
| format | Article |
| id | doaj.art-7133add646a249d7b65232fbf92f8021 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T03:08:42Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7133add646a249d7b65232fbf92f80212022-12-22T03:05:08ZengElsevierCell Reports2211-12472017-09-0120122820283210.1016/j.celrep.2017.08.057Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1Archis Bagati0Anna Bianchi-Smiraglia1Sudha Moparthy2Kateryna Kolesnikova3Emily E. Fink4Brittany C. Lipchick5Masha Kolesnikova6Peter Jowdy7Anthony Polechetti8Amin Mahpour9Jason Ross10Joseph A. Wawrzyniak11Dong Hyun Yun12Gyorgy Paragh13Nadezhda I. Kozlova14Albert E. Berman15Jianmin Wang16Song Liu17Michael J. Nemeth18Mikhail A. Nikiforov19Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USAOrekhovich Institute of Biomedical Chemistry, Moscow 119121, RussiaOrekhovich Institute of Biomedical Chemistry, Moscow 119121, RussiaDepartment of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USADepartment of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USALineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) transcription of the N-cadherin gene (CDH2). We demonstrate that FOXQ1 interacts with nuclear β-catenin and TLE proteins, and the β-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear β-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes.http://www.sciencedirect.com/science/article/pii/S2211124717311828melanomacarcinomaFOXQ1N-cadherinβ-cateninepithelial-to-mesenchymal transitioninvasionmetastasisdifferentiation |
| spellingShingle | Archis Bagati Anna Bianchi-Smiraglia Sudha Moparthy Kateryna Kolesnikova Emily E. Fink Brittany C. Lipchick Masha Kolesnikova Peter Jowdy Anthony Polechetti Amin Mahpour Jason Ross Joseph A. Wawrzyniak Dong Hyun Yun Gyorgy Paragh Nadezhda I. Kozlova Albert E. Berman Jianmin Wang Song Liu Michael J. Nemeth Mikhail A. Nikiforov Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1 Cell Reports melanoma carcinoma FOXQ1 N-cadherin β-catenin epithelial-to-mesenchymal transition invasion metastasis differentiation |
| title | Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1 |
| title_full | Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1 |
| title_fullStr | Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1 |
| title_full_unstemmed | Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1 |
| title_short | Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1 |
| title_sort | melanoma suppressor functions of the carcinoma oncogene foxq1 |
| topic | melanoma carcinoma FOXQ1 N-cadherin β-catenin epithelial-to-mesenchymal transition invasion metastasis differentiation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717311828 |
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