PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer

Csolle, Mariah P; Ooms, Lisa M; Papa, Antonella; Mitchell, Christina A.

doi:10.3390/ijms21239189

Cited by 39 publications

(39 citation statements)

References 145 publications

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“…Hence PI3K/Akt signaling appears to be a target of Ltp1, but acting through an inhibitor to cause increased phosphorylation. The phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) preferentially dephosphorylates phosphoinositide substrates and thus inhibits PI3K action by negatively regulating intracellular levels of phosphatidylinositol-3,4,5-trisphosphate [ 67 ]. Several lines of evidence indicated that dephosphorylation of PTEN by Ltp1 increases proteasomal degradation, thus relieving suppression of PI3K/Akt.…”

Section: Discussionmentioning

confidence: 99%

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

et al. 2021

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Tyrosine phosphatases are often weaponized by bacteria colonizing mucosal barriers to manipulate host cell signal transduction pathways. Porphyromonas gingivalis is a periodontal pathogen and emerging oncopathogen which interferes with gingival epithelial cell proliferation and migration, and induces a partial epithelial mesenchymal transition. P. gingivalis produces two tyrosine phosphatases, and we show here that the low molecular weight tyrosine phosphatase, Ltp1, is secreted within gingival epithelial cells and translocates to the nucleus. An ltp1 mutant of P. gingivalis showed a diminished ability to induce epithelial cell migration and proliferation. Ltp1 was also required for the transcriptional upregulation of Regulator of Growth and Cell Cycle (RGCC), one of the most differentially expressed genes in epithelial cells resulting from P. gingivalis infection. A phosphoarray and siRNA showed that P. gingivalis controlled RGCC expression through Akt, which was activated by phosphorylation on S473. Akt activation is opposed by PTEN, and P. gingivalis decreased the amount of PTEN in epithelial cells. Ectopically expressed Ltp1 bound to PTEN, and reduced phosphorylation of PTEN at Y336 which controls proteasomal degradation. Ltp-1 induced loss of PTEN stability was prevented by chemical inhibition of the proteosome. Knockdown of RGCC suppressed upregulation of Zeb2 and mesenchymal markers by P. gingivalis. RGCC inhibition was also accompanied by a reduction in production of the proinflammatory cytokine IL-6 in response to P. gingivalis. Elevated IL-6 levels can contribute to periodontal destruction, and the ltp1 mutant of P. gingivalis incited less bone loss compared to the parental strain in a murine model of periodontal disease. These results show that P. gingivalis can deliver Ltp1 within gingival epithelial cells, and establish PTEN as the target for Ltp1 phosphatase activity. Disruption of the Akt1/RGCC signaling axis by Ltp1 facilitates P. gingivalis-induced increases in epithelial cell migration, proliferation, EMT and inflammatory cytokine production.

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Section: Discussionmentioning

confidence: 99%

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

et al. 2021

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“…In gliomas, miR-492-3p negatively regulates the expression of PTEN, whereas circNALCN positively regulates the expression of PTEN. Previous studies have shown that PTEN acts as a tumor suppressor in most human tumors, such as pancreatic cancer, HCC, and breast cancer [ 32 – 34 ]. Decreased PTEN expression is typically associated with aggressive tumors and a worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression

et al. 2021

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Background An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in the regulation of tumor progression. Therefore, we explored the expression characteristics, function, and related mechanism of the newly identified circNALCN in glioma. Methods RNA sequencing was used to analyze the expression profiles of circRNAs in brain tissue from five glioma cases and four normal controls. Quantitative real-time polymerase chain reaction was implemented to examine the levels of circNALCN, miR-493-3p, and phosphatase and tensin homolog (PTEN). Cell counting kit 8 assays were performed to analyze cell proliferation, and cell migration was assessed by the wound healing test and Transwell assay. Dual-luciferase reporter, fluorescence in situ hybridization, and RNA pulldown assays were performed to confirm the role of circNALCN as an miR-493-3p sponge, weakening the inhibitory effect of miR-493-3p on target PTEN expression. Results The downregulated expression of circNALCN was observed in both glioma tissues and cell lines. CircNALCN expression was negatively correlated with World Health Organization grade and overall survival in patients with glioma. Functionally, the overexpression of circNALCN significantly inhibited the proliferation and migration of glioma cells, whereas miR-493-3p mimics counteracted these effects. The mechanistic analysis demonstrated that circNALCN acted as a competing endogenous RNA for miR-493-3p to relieve the repressive effects of miR-493-3p on its target, PTEN, suppressing glioma tumorigenesis. Conclusions CircNALCN inhibits the progression of glioma through the miR-493-3p/PTEN axis, providing a developable biomarker and therapeutic target for glioma patients.

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“…GUCY2C, which encodes the guanylate cyclase C receptor, is known to reduce stem cell vulnerability to environmental damage by modulating the endoplasmic reticulum stress response ( Kraft et al, 2017 ). SYNJ2 (Synaptojanin 2) has been identified as a player in epidermal growth factor receptor (EGFR) recycling and EGF-dependent migration ( Csolle et al, 2020 ). ANKRD13B codes for a member of the Ankyrin repeat domain-containing protein 13 family and has recently been described as interfering with regulation of the endosome-to-lysosome trafficking of Caveolin 1 (Cav-1) ( Burana et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

PGE2 Supplementation of Oocyte Culture Media Improves the Developmental and Cryotolerance Performance of Bovine Blastocysts Derived From a Serum-Free in vitro Production System, Mirroring the Inner Cell Mass Transcriptome

Charpigny

Guienne

Richard

et al. 2021

Front. Cell Dev. Biol.

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The culture media used throughout the in vitro production (IVP) of bovine embryos remain complex. The serum added to culture media in order to improve embryo development negatively impacts the cryotolerance of blastocysts. Periconceptional prostaglandin E2 (PGE2) signaling is known to exert prosurvival effects on in vitro-generated blastocysts. The purpose of the present study was to evaluate the effects on developmental and cryotolerance performance of a serum-free (SF) IVP system that included defined oocyte culture media supplemented or not with PGE2, versus serum-containing (SC) IVP. RNA-sequencing analysis was used to examine the gene expression of ICM derived under the different IVP conditions. We assessed the degree of cryotolerance of grade-I blastocysts during a three-day post-thaw culture by measuring survival and hatching rates, counting trophectoderm and inner cell mass (ICM) blastomere numbers. We also determined the proportion of ICM cells expressing octamer-binding transcription factor 4 protein (OCT4/POU5F1). We showed that grade-I blastocyst development rates under SF + PGE2 conditions were similar to those obtained under SC conditions, although the cleavage rate remained significantly lower. SC IVP conditions induced changes to ICM gene expression relative to several metabolic processes, catabolic activities, cell death and apoptosis. These alterations were associated with significantly higher levels of ICM cell death at day 7 post-fertilization, and lower survival and hatching rates after thawing. SF IVP conditions supplemented or not with PGE2 induced changes to ICM gene expression related to DNA replication, metabolism and double-strand break repair processes, and were associated with significantly larger ICM cell populations after thawing. SF + PGE2 IVP induced changes to ICM gene expression related to epigenetic regulation and were associated with a significantly higher proportion of ICM cells expressing OCT4. For the first time, our study thus offers a comprehensive analysis of the ICM transcriptome regulated by IVP culture conditions in terms of the cellular changes revealed during culture for three days after thawing.

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PTEN and Other PtdIns(3,4,5)P3 Lipid Phosphatases in Breast Cancer

Cited by 39 publications

References 145 publications

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

CircRNA NALCN acts as an miR-493-3p sponge to regulate PTEN expression and inhibit glioma progression

PGE2 Supplementation of Oocyte Culture Media Improves the Developmental and Cryotolerance Performance of Bovine Blastocysts Derived From a Serum-Free in vitro Production System, Mirroring the Inner Cell Mass Transcriptome

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