PP007. Effects of STAT1 suppression on ERK1/2 in trophoblastic cells

Sousa, Francisco Lázaro Pereira de; Prieto, D.M. Morales; Prieto, Stephanie Ospina; Chaiwangyen, Wittaya; Daher, Sílvia; Sass, Nelson; Markert, Udo R.

doi:10.1016/j.preghy.2012.04.118

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Significant reduction in phosphorylation of ERK½ and STAT3 at ser 727 was observed in STAT1 silenced cells after EGF treatment, which can possibly be due to absence of phosphorylated STAT1 ser 727 in STAT1 silenced cells ( Fig 8 ). Similar, reduced ERK½ phosphorylation after STAT1 silencing and inhibition of STAT1 binding by Fludarabine has been observed previously [ 50 ], though the mechanism has not been elaborated. STAT1 and STAT3 phosphorylated forms can form heterodimers with each other [ 51 ].…”

Section: Discussionsupporting

confidence: 75%

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Malik¹,

Pal²,

Gupta³

2017

PLoS ONE

View full text Add to dashboard Cite

Invasion of trophoblast cells is spatio-temporally regulated by various cytokines and growth factors. In pregnancy, complications like preeclampsia, shallow invasion of trophoblast cells and low amounts of epidermal growth factor (EGF) have been reported. In the present study, regulatory mechanisms associated with EGF-mediated invasion in HTR-8/SVneo trophoblastic cells have been delineated. Treatment of HTR-8/SVneo cells with EGF (10 ng/ml) led to eight fold increase (p < 0.05) in invasion. Increased invasion of HTR-8/SVneo cells by EGF was associated with an increase in phosphorylation of ERK½. In addition, significant phosphorylation of STAT1 (ser 727) and STAT3 (both tyr 705 and ser 727 residues) was also observed, accompanied by a decrease in total STAT1. Inhibition of ERK½ phosphorylation by U0126 (10 μM) led to a significant decrease in EGF-mediated invasion with simultaneous decrease in the phosphorylated forms of STAT3 and STAT1. Decrease in total STAT1 was also reversed on inhibition of ERK½. Interestingly, inhibition of STAT3 by siRNA led to a significant decrease in EGF-mediated invasion of HTR-8/SVneo cells and phosphorylation of STAT1, but it did not have any effect on the activation of ERK½. On the other hand, inhibition of STAT1 by siRNA, also led to a significant decrease in the EGF-mediated invasion of HTR-8/SVneo cells, showed concomitant decrease in ERK½ phosphorylation and STAT3 phosphorylation at ser 727 residue. These results suggest cross-communication between ERK½ and JAK-STAT pathways during EGF-mediated increase in invasion of trophoblast cells; phosphorylation at ser 727 residue of both STAT3 and STAT1 appears to be critical.

show abstract

Section: Discussionsupporting

confidence: 75%

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Malik¹,

Pal²,

Gupta³

2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Invasion‐promoting effect of IL‐11 in JEG‐3 cells is also triggered through STAT3 phosphorylation both at tyrosine and at serine residues . In addition to STAT3, activation of STAT1 has also been reported in HTR‐8/SVneo and JEG‐3 following treatment with LIF; inhibition of STAT1 led to slight decrease in invasion . Another family of STAT proteins involved in promotion of trophoblast invasion is STAT5; human placental growth hormone (hPGH) activates STAT5 through JAK2 and stimulates invasion in primary EVT .…”

Section: Signaling In Trophoblast Invasion and Migrationmentioning

confidence: 99%

Cell Signaling Pathways Involved During Invasion and Syncytialization of Trophoblast Cells

Gupta

Malhotra

Malik

et al. 2015

American J Rep Immunol

167

116

View full text Add to dashboard Cite

Implantation involves an extensive cross talk between the trophoblast cells and the receptive endometrium through embryonic as well as endometrial-derived factors that regulate the invasion and migration of trophoblast cells and also syncytia formation. Any aberration in this highly regulated process may lead to pregnancy complications such as preeclampsia, intrauterine growth restriction, or even pregnancy failure. How various cytokines and growth factors act by activating various cell signaling pathways leading to the expression of the effector molecules have been reviewed, which control invasion and migration of trophoblast cells and syncytialization. The gaps in our current understanding of the various signaling pathways, activated by different cytokines/growth factors, their possible cross talk for optimized effector function(s), and future prospects in this field have been discussed.

show abstract

“…In addition, ‘JAK-STAT signaling’, which is key for the cytokine- and growth factor-mediated modulation of cell proliferation and migration, was also found to be changed only in choriocarcinoma cells. This may be in line with the effects of a potentially immunosuppressive microenvironment compared to those in normal gestation on trophoblasts malignant behavior [ 78 , 79 , 80 , 81 , 82 , 83 ].…”

Section: Discussionmentioning

confidence: 52%

Epigenetic Dysregulation of Trophoblastic Gene Expression in Gestational Trophoblastic Disease

et al. 2021

View full text Add to dashboard Cite

Gestational trophoblastic diseases (GTDs) have not been investigated for their epigenetic marks and consequent transcriptomic changes. Here, we analyzed genome-wide DNA methylation and transcriptome data to reveal the epigenetic basis of disease pathways that may lead to benign or malignant GTDs. RNA-Seq, mRNA microarray, and Human Methylation 450 BeadChip data from complete moles and choriocarcinoma cells were bioinformatically analyzed. Paraffin-embedded tissues from complete moles and control placentas were used for tissue microarray construction, DNMT3B immunostaining and immunoscoring. We found that DNA methylation increases with disease severity in GTDs. Differentially expressed genes are mainly upregulated in moles while predominantly downregulated in choriocarcinoma. DNA methylation principally influences the gene expression of villous trophoblast differentiation-related or predominantly placenta-expressed genes in moles and choriocarcinoma cells. Affected genes in these subsets shared focal adhesion and actin cytoskeleton pathways in moles and choriocarcinoma. In moles, cell cycle and differentiation regulatory pathways, essential for trophoblast/placental development, were enriched. In choriocarcinoma cells, hormone biosynthetic, extracellular matrix-related, hypoxic gene regulatory, and differentiation-related signaling pathways were enriched. In moles, we found slight upregulation of DNMT3B protein, a developmentally important de novo DNA methylase, which is strongly overexpressed in choriocarcinoma cells that may partly be responsible for the large DNA methylation differences. Our findings provide new insights into the shared and disparate molecular pathways of disease in GTDs and may help in designing new diagnostic and therapeutic tools.

show abstract

PP007. Effects of STAT1 suppression on ERK1/2 in trophoblastic cells

Cited by 4 publications

References 0 publications

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion

Cell Signaling Pathways Involved During Invasion and Syncytialization of Trophoblast Cells

Epigenetic Dysregulation of Trophoblastic Gene Expression in Gestational Trophoblastic Disease

Contact Info

Product

Resources

About