The interplay between intracellular progesterone receptor and PKC plays a key role in migration and invasion of human glioblastoma cells

Marquina-Sánchez, Brenda; González-Jorge, Jesús; Hansberg-Pastor, Valeria; Wegman-Ostrosky, Talía; Baranda-Ávila, Noemi; Mejía-Pérez, Sonia Iliana; González-Arenas, Aliesha

doi:10.1016/j.jsbmb.2016.10.001

Cited by 16 publications

(13 citation statements)

References 51 publications

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“…Recent studies describe that GBM cells express both mPRα and mPRβ, and that the specific activation of mPRα by the selective agonist Org OD 02-0 induces cell proliferation and invasion (Valadez-Cosmes et al, 2015; González-Orozco et al, 2018). Similar effects are seen when the PR is activated via ligand-independent activation by protein kinase C (González-Arenas et al, 2015; Marquina-Sánchez et al, 2017), suggesting an interplay between the classical and non-classical mechanisms of progesterone action in GBM tumors progression.…”

Section: Progesterone Actions During Cns Developmentmentioning

confidence: 84%

Progesterone Actions During Central Nervous System Development

González-Orozco

Camacho‐Arroyo

2019

Front. Neurosci.

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Although progesterone is a steroid hormone mainly associated with female reproductive functions, such as uterine receptivity and maintenance of pregnancy, accumulating data have shown its physiological actions to extend to several non-reproductive functions in the central nervous system (CNS) both in males and females. In fact, progesterone is de novo synthesized in specific brain regions by neurons and glial cells and is involved in the regulation of various molecular and cellular processes underlying myelination, neuroprotection, neuromodulation, learning and memory, and mood. Furthermore, progesterone has been reported to be implicated in critical developmental events, such as cell differentiation and neural circuits formation. This view is supported by the increase in progesterone synthesis observed during pregnancy in both the placenta and the fetal brain. In the present review, we will focus on progesterone actions during CNS development.

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Section: Progesterone Actions During Cns Developmentmentioning

confidence: 84%

Progesterone Actions During Central Nervous System Development

González-Orozco

Camacho‐Arroyo

2019

Front. Neurosci.

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“…For example, PDPK1 (3-phosphoinositide dependent protein kinase 1) dysregulated expression is known to damage glucose metabolism, cell migration, cell survival and neural plasticity (Scheid et al, 2005; Park et al, 2013). Under-expression of PRKCA (Protein kinase C alpha) is linked with modulation of apoptotic signaling and cell proliferation while Src (SRC proto-oncogene, non-receptor tyrosine kinase), which has a role in actin dynamics in U-251 cells, is associated with the disruption of cell migration (Angers-Loustau et al, 2004; Marquina-Sanchez et al, 2017). In addition, the under-expression of GFRA1 (GDNF family receptor alpha 1) by ZIKV can disrupt its binding with GDNF (glial cell-line derived neurotrophic factor), dysregulating the process of cell differentiation and proliferation indirectly (Takashima et al, 2015; Ayanlaja et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance

2019

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The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015. Recent studies have reported cases in Europe, Oceania and Latin America. In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern. Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barré syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo)encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis. Astrocytes are one of the most abundant cells in the CNS. They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV. In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.

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“…Among other functions, it is directly related to regulating the transcriptional activity of this receptor and the degradation by the proteasome (59,60). Serine and threonine phosphorylation of PR has been widely investigated (60)(61)(62); however, there are no reports about PR tyrosine phosphorylation. Therefore, we performed an in silico analysis in three databases to search putative phosphorylation sites of cSrc over PR.…”

Section: Discussionmentioning

confidence: 99%

Intracellular Progesterone Receptor and cSrc Protein Working Together to Regulate the Activity of Proteins Involved in Migration and Invasion of Human Glioblastoma Cells

2021

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Glioblastomas are the most common and aggressive primary brain tumors in adults, and patients with glioblastoma have a median survival of 15 months. Some alternative therapies, such as Src family kinase inhibitors, have failed presumably because other signaling pathways compensate for their effects. In the last ten years, it has been proven that sex hormones such as progesterone (P4) can induce growth, migration, and invasion of glioblastoma cells through its intracellular progesterone receptor (PR), which is mostly known for its role as a transcription factor, but it can also induce non-genomic actions. These non-classic actions are, in part, a consequence of its interaction with cSrc, which plays a significant role in the progression of glioblastomas. We studied the relation between PR and cSrc, and its effects in human glioblastoma cells. Our results showed that P4 and R5020 (specific PR agonist) activated cSrc protein since both progestins increased the p-cSrc (Y416)/cSrc ratio in U251 and U87 human glioblastoma derived cell lines. When siRNA against the PR gene was used, the activation of cSrc by P4 was abolished. The co-immunoprecipitation assay showed that cSrc and PR interact in U251 cells. P4 treatment also promoted the increase in the p-Fak (Y397) (Y576/577)/Fak and the decrease in p-Paxillin (Y118)/Paxillin ratio, which are significant components of the focal adhesion complex and essential for migration and invasion processes. A siRNA against cSrc gene blocked the increase in the p-Fak (Y576/Y577)/Fak ratio and the migration induced by P4, but not the decrease in p-Paxillin (Y118)/Paxillin ratio. We analyzed the potential role of cSrc over PR phosphorylation in three databases, and one putative tyrosine residue in the amino acid 87 of PR was found. Our results showed that P4 induces the activation of cSrc protein through its PR. The latter and cSrc could interact in a bidirectional mode for regulating the activity of proteins involved in migration and invasion of glioblastomas.

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The interplay between intracellular progesterone receptor and PKC plays a key role in migration and invasion of human glioblastoma cells

Cited by 16 publications

References 51 publications

Progesterone Actions During Central Nervous System Development

Progesterone Actions During Central Nervous System Development

Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance

Intracellular Progesterone Receptor and cSrc Protein Working Together to Regulate the Activity of Proteins Involved in Migration and Invasion of Human Glioblastoma Cells

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