p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells
P53 is a critical tumor suppressor that protects the integrity of genome and prevents cells from malignant transformation, including metastases. One of the driving forces behind the onset of metastases is the epithelial to mesenchymal transition (EMT) program. Zeb1 is one of the key transcription fa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/9806 |
| _version_ | 1797594377639428096 |
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| author | Sergey E. Parfenyev Sergey V. Shabelnikov Elena N. Tolkunova Nickolai A. Barlev Alexey G. Mittenberg |
| author_facet | Sergey E. Parfenyev Sergey V. Shabelnikov Elena N. Tolkunova Nickolai A. Barlev Alexey G. Mittenberg |
| author_sort | Sergey E. Parfenyev |
| collection | DOAJ |
| description | P53 is a critical tumor suppressor that protects the integrity of genome and prevents cells from malignant transformation, including metastases. One of the driving forces behind the onset of metastases is the epithelial to mesenchymal transition (EMT) program. Zeb1 is one of the key transcription factors that govern EMT (TF-EMT). Therefore, the interaction and mutual influence of p53 and Zeb1 plays a critical role in carcinogenesis. Another important feature of tumors is their heterogeneity mediated by the presence of so-called cancer stem cells (CSCs). To this end, we have developed a novel fluorescent reporter-based approach to enrich the population of CSCs in MCF7 cells with inducible expression of Zeb1. Using these engineered cell lines, we studied the effect of p53 on Zeb1 interactomes isolated from both CSCs and regular cancer cells. By employing co-immunoprecipitations followed by mass spectrometry, we found that the composition of Zeb1 interactome was affected not only by the p53 status but also by the level of Oct4/Sox2 expression, indicating that stemness likely affects the specificity of Zeb1 interactions. This study, together with other proteomic studies of TF-EMT interactomes, provides a framework for future molecular analyses of biological functions of Zeb1 at all stages of oncogenesis. |
| first_indexed | 2024-03-11T02:22:51Z |
| format | Article |
| id | doaj.art-cb47e00f21cd484e8a837d6d7331b5a9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:22:51Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cb47e00f21cd484e8a837d6d7331b5a92023-11-18T10:44:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012412980610.3390/ijms24129806p53 Affects Zeb1 Interactome of Breast Cancer Stem CellsSergey E. Parfenyev0Sergey V. Shabelnikov1Elena N. Tolkunova2Nickolai A. Barlev3Alexey G. Mittenberg4Institute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, RussiaInstitute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, RussiaInstitute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, RussiaInstitute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, RussiaInstitute of Cytology of the Russian Academy of Sciences, St. Petersburg 194064, RussiaP53 is a critical tumor suppressor that protects the integrity of genome and prevents cells from malignant transformation, including metastases. One of the driving forces behind the onset of metastases is the epithelial to mesenchymal transition (EMT) program. Zeb1 is one of the key transcription factors that govern EMT (TF-EMT). Therefore, the interaction and mutual influence of p53 and Zeb1 plays a critical role in carcinogenesis. Another important feature of tumors is their heterogeneity mediated by the presence of so-called cancer stem cells (CSCs). To this end, we have developed a novel fluorescent reporter-based approach to enrich the population of CSCs in MCF7 cells with inducible expression of Zeb1. Using these engineered cell lines, we studied the effect of p53 on Zeb1 interactomes isolated from both CSCs and regular cancer cells. By employing co-immunoprecipitations followed by mass spectrometry, we found that the composition of Zeb1 interactome was affected not only by the p53 status but also by the level of Oct4/Sox2 expression, indicating that stemness likely affects the specificity of Zeb1 interactions. This study, together with other proteomic studies of TF-EMT interactomes, provides a framework for future molecular analyses of biological functions of Zeb1 at all stages of oncogenesis.https://www.mdpi.com/1422-0067/24/12/9806breast cancercancer stem cellsepithelial-to-mesenchymal transition (EMT)metastasisp53Zeb1 |
| spellingShingle | Sergey E. Parfenyev Sergey V. Shabelnikov Elena N. Tolkunova Nickolai A. Barlev Alexey G. Mittenberg p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells International Journal of Molecular Sciences breast cancer cancer stem cells epithelial-to-mesenchymal transition (EMT) metastasis p53 Zeb1 |
| title | p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells |
| title_full | p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells |
| title_fullStr | p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells |
| title_full_unstemmed | p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells |
| title_short | p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells |
| title_sort | p53 affects zeb1 interactome of breast cancer stem cells |
| topic | breast cancer cancer stem cells epithelial-to-mesenchymal transition (EMT) metastasis p53 Zeb1 |
| url | https://www.mdpi.com/1422-0067/24/12/9806 |
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