SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells
SELENOF expression is significantly lower in aggressive breast tumors compared to normal tissue, indicating that its reduction or loss may drive breast tumorigenesis. Deletion of SELENOF in non-tumorigenic immortalized breast epithelial MCF-10A cells resulted in enhanced proliferation, both in adher...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-07-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/14/3671 |
| _version_ | 1797589872460955648 |
|---|---|
| author | Roudy C. Ekyalongo Brenna Flowers Tanu Sharma Alexandra Zigrossi An Zhang Anaisa Quintanilla-Arteaga Kanishka Singh Irida Kastrati |
| author_facet | Roudy C. Ekyalongo Brenna Flowers Tanu Sharma Alexandra Zigrossi An Zhang Anaisa Quintanilla-Arteaga Kanishka Singh Irida Kastrati |
| author_sort | Roudy C. Ekyalongo |
| collection | DOAJ |
| description | SELENOF expression is significantly lower in aggressive breast tumors compared to normal tissue, indicating that its reduction or loss may drive breast tumorigenesis. Deletion of SELENOF in non-tumorigenic immortalized breast epithelial MCF-10A cells resulted in enhanced proliferation, both in adherent culture and matrix-assisted three-dimmensional (3D) growth. Modulation of SELENOF in vitro through deletion or overexpression corresponded to changes in the cell-cycle regulators p21 and p27, which is consistent with breast tumor expression data from the METABRIC patient database. Together, these findings indicate that SELENOF affects both proliferation and cell death in normal epithelial and breast cancer cells, largely through the regulation of p21 and p27. In glandular cancers like breast cancer, the filling of luminal space is one of the hallmarks of early tumorigenesis. Loss of SELENOF abrogated apoptosis and autophagy, which are required for the formation of hollow acini in MCF-10A cells in matrix-assisted 3D growth, resulting in luminal filling. Conversely, overexpression of SELENOF induced cell death via apoptosis and autophagy. In conclusion, these findings are consistent with the notion that SELENOF is a breast tumor suppressor, and its loss contributes to breast cancer etiology. |
| first_indexed | 2024-03-11T01:12:17Z |
| format | Article |
| id | doaj.art-0de84271aaea4e52afe9e9a2d4fa6085 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T01:12:17Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0de84271aaea4e52afe9e9a2d4fa60852023-11-18T18:42:27ZengMDPI AGCancers2072-66942023-07-011514367110.3390/cancers15143671SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer CellsRoudy C. Ekyalongo0Brenna Flowers1Tanu Sharma2Alexandra Zigrossi3An Zhang4Anaisa Quintanilla-Arteaga5Kanishka Singh6Irida Kastrati7Department of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USADepartment of Cancer Biology, Loyola University Chicago, Maywood, IL 60153, USASELENOF expression is significantly lower in aggressive breast tumors compared to normal tissue, indicating that its reduction or loss may drive breast tumorigenesis. Deletion of SELENOF in non-tumorigenic immortalized breast epithelial MCF-10A cells resulted in enhanced proliferation, both in adherent culture and matrix-assisted three-dimmensional (3D) growth. Modulation of SELENOF in vitro through deletion or overexpression corresponded to changes in the cell-cycle regulators p21 and p27, which is consistent with breast tumor expression data from the METABRIC patient database. Together, these findings indicate that SELENOF affects both proliferation and cell death in normal epithelial and breast cancer cells, largely through the regulation of p21 and p27. In glandular cancers like breast cancer, the filling of luminal space is one of the hallmarks of early tumorigenesis. Loss of SELENOF abrogated apoptosis and autophagy, which are required for the formation of hollow acini in MCF-10A cells in matrix-assisted 3D growth, resulting in luminal filling. Conversely, overexpression of SELENOF induced cell death via apoptosis and autophagy. In conclusion, these findings are consistent with the notion that SELENOF is a breast tumor suppressor, and its loss contributes to breast cancer etiology.https://www.mdpi.com/2072-6694/15/14/3671breast cancerselenoprotein F (SELENOF)tumor suppressoracinar growthproliferationcell death |
| spellingShingle | Roudy C. Ekyalongo Brenna Flowers Tanu Sharma Alexandra Zigrossi An Zhang Anaisa Quintanilla-Arteaga Kanishka Singh Irida Kastrati SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells Cancers breast cancer selenoprotein F (SELENOF) tumor suppressor acinar growth proliferation cell death |
| title | SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells |
| title_full | SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells |
| title_fullStr | SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells |
| title_full_unstemmed | SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells |
| title_short | SELENOF Controls Proliferation and Cell Death in Breast-Derived Immortalized and Cancer Cells |
| title_sort | selenof controls proliferation and cell death in breast derived immortalized and cancer cells |
| topic | breast cancer selenoprotein F (SELENOF) tumor suppressor acinar growth proliferation cell death |
| url | https://www.mdpi.com/2072-6694/15/14/3671 |
| work_keys_str_mv | AT roudycekyalongo selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT brennaflowers selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT tanusharma selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT alexandrazigrossi selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT anzhang selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT anaisaquintanillaarteaga selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT kanishkasingh selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells AT iridakastrati selenofcontrolsproliferationandcelldeathinbreastderivedimmortalizedandcancercells |