LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells
Lysophosphatidic acid (LPA) induces a wide range of cellular processes and its signaling is increased in several cancers including glioblastoma (GBM), a high-grade astrocytoma, which is the most common malignant brain tumor. LPA<sub>1</sub> receptor is expressed in GBM cells and its sign...
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MDPI AG
2021-04-01
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| author | Silvia Anahi Valdés-Rives Denisse Arcos-Montoya Marisol de la Fuente-Granada Carmen J. Zamora-Sánchez Luis Enrique Arias-Romero Olga Villamar-Cruz Ignacio Camacho-Arroyo Sonia M. Pérez-Tapia Aliesha González-Arenas |
| author_facet | Silvia Anahi Valdés-Rives Denisse Arcos-Montoya Marisol de la Fuente-Granada Carmen J. Zamora-Sánchez Luis Enrique Arias-Romero Olga Villamar-Cruz Ignacio Camacho-Arroyo Sonia M. Pérez-Tapia Aliesha González-Arenas |
| author_sort | Silvia Anahi Valdés-Rives |
| collection | DOAJ |
| description | Lysophosphatidic acid (LPA) induces a wide range of cellular processes and its signaling is increased in several cancers including glioblastoma (GBM), a high-grade astrocytoma, which is the most common malignant brain tumor. LPA<sub>1</sub> receptor is expressed in GBM cells and its signaling pathways activate protein kinases C (PKCs). A downstream target of PKC, involved in GBM progression, is the intracellular progesterone receptor (PR), which can be phosphorylated by this enzyme, increasing its transcriptional activity. Interestingly, in GBM cells, PKCα isotype translocates to the nucleus after LPA stimulation, resulting in an increase in PR phosphorylation. In this study, we determined that LPA<sub>1</sub> receptor activation induces protein-protein interaction between PKCα and PR in human GBM cells; this interaction increased PR phosphorylation in serine400. Moreover, LPA treatment augmented <i>VEGF</i> transcription, a known PR target. This effect was blocked by the PR selective modulator RU486; also, the activation of LPA<sub>1</sub>/PR signaling promoted migration of GBM cells. Interestingly, using TCGA data base, we found that mRNA expression of <i>LPAR1</i> increases according to tumor malignancy and correlates with a lower survival in grade III astrocytomas. These results suggest that LPA<sub>1</sub>/PR pathway regulates GBM progression. |
| first_indexed | 2024-03-10T12:37:14Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:37:14Z |
| publishDate | 2021-04-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-f11f9f86c3a3449e88625deb570ba3ff2023-11-21T14:13:53ZengMDPI AGCells2073-44092021-04-0110480710.3390/cells10040807LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma CellsSilvia Anahi Valdés-Rives0Denisse Arcos-Montoya1Marisol de la Fuente-Granada2Carmen J. Zamora-Sánchez3Luis Enrique Arias-Romero4Olga Villamar-Cruz5Ignacio Camacho-Arroyo6Sonia M. Pérez-Tapia7Aliesha González-Arenas8Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, MexicoDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, MexicoDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, MexicoUnidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, MexicoUnidad de Investigación en Biomedicina (UBIMED), Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, 54090 Estado de México, MexicoUnidad de Investigación en Biomedicina (UBIMED), Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, 54090 Estado de México, MexicoUnidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, MexicoUnidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11350 Ciudad de México, MexicoDepartamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), 04510 Ciudad de México, MexicoLysophosphatidic acid (LPA) induces a wide range of cellular processes and its signaling is increased in several cancers including glioblastoma (GBM), a high-grade astrocytoma, which is the most common malignant brain tumor. LPA<sub>1</sub> receptor is expressed in GBM cells and its signaling pathways activate protein kinases C (PKCs). A downstream target of PKC, involved in GBM progression, is the intracellular progesterone receptor (PR), which can be phosphorylated by this enzyme, increasing its transcriptional activity. Interestingly, in GBM cells, PKCα isotype translocates to the nucleus after LPA stimulation, resulting in an increase in PR phosphorylation. In this study, we determined that LPA<sub>1</sub> receptor activation induces protein-protein interaction between PKCα and PR in human GBM cells; this interaction increased PR phosphorylation in serine400. Moreover, LPA treatment augmented <i>VEGF</i> transcription, a known PR target. This effect was blocked by the PR selective modulator RU486; also, the activation of LPA<sub>1</sub>/PR signaling promoted migration of GBM cells. Interestingly, using TCGA data base, we found that mRNA expression of <i>LPAR1</i> increases according to tumor malignancy and correlates with a lower survival in grade III astrocytomas. These results suggest that LPA<sub>1</sub>/PR pathway regulates GBM progression.https://www.mdpi.com/2073-4409/10/4/807glioblastomaLPA<sub>1</sub> receptorprotein kinase C αprogesterone receptor |
| spellingShingle | Silvia Anahi Valdés-Rives Denisse Arcos-Montoya Marisol de la Fuente-Granada Carmen J. Zamora-Sánchez Luis Enrique Arias-Romero Olga Villamar-Cruz Ignacio Camacho-Arroyo Sonia M. Pérez-Tapia Aliesha González-Arenas LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells Cells glioblastoma LPA<sub>1</sub> receptor protein kinase C α progesterone receptor |
| title | LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells |
| title_full | LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells |
| title_fullStr | LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells |
| title_full_unstemmed | LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells |
| title_short | LPA<sub>1</sub> Receptor Promotes Progesterone Receptor Phosphorylation through PKCα in Human Glioblastoma Cells |
| title_sort | lpa sub 1 sub receptor promotes progesterone receptor phosphorylation through pkcα in human glioblastoma cells |
| topic | glioblastoma LPA<sub>1</sub> receptor protein kinase C α progesterone receptor |
| url | https://www.mdpi.com/2073-4409/10/4/807 |
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