TY - JOUR
T1 - Lpa1 receptor promotes progesterone receptor phosphorylation through pkcα in human glioblastoma cells
AU - Valdés-Rives, Silvia Anahi
AU - Arcos-Montoya, Denisse
AU - de la Fuente-Granada, Marisol
AU - Zamora-Sánchez, Carmen J.
AU - Arias-Romero, Luis Enrique
AU - Villamar-Cruz, Olga
AU - Camacho-Arroyo, Ignacio
AU - Pérez-Tapia, Sonia M.
AU - González-Arenas, Aliesha
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/4
Y1 - 2021/4
N2 - 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. LPA1 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 LPA1 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 VEGF transcription, a known PR target. This effect was blocked by the PR selective modulator RU486; also, the activation of LPA1/PR signaling promoted migration of GBM cells. Interestingly, using TCGA data base, we found that mRNA expression of LPAR1 increases according to tumor malignancy and correlates with a lower survival in grade III astrocytomas. These results suggest that LPA1/PR pathway regulates GBM progression.
AB - 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. LPA1 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 LPA1 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 VEGF transcription, a known PR target. This effect was blocked by the PR selective modulator RU486; also, the activation of LPA1/PR signaling promoted migration of GBM cells. Interestingly, using TCGA data base, we found that mRNA expression of LPAR1 increases according to tumor malignancy and correlates with a lower survival in grade III astrocytomas. These results suggest that LPA1/PR pathway regulates GBM progression.
KW - Glioblastoma
KW - LPA receptor
KW - Progesterone receptor
KW - Protein kinase C α
UR - http://www.scopus.com/inward/record.url?scp=85105208203&partnerID=8YFLogxK
U2 - 10.3390/cells10040807
DO - 10.3390/cells10040807
M3 - Artículo
C2 - 33916643
AN - SCOPUS:85105208203
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 4
M1 - 807
ER -