Glucose-Induced Oxidative Stress Reduces Proliferation in Embryonic Stem Cells via FOXO3A/β-Catenin-Dependent Transcription of p21cip1

Descalzo, Darcie L. McClelland; Satoorian, Tiffany S.; Walker, Lauren M.; Sparks, Nicole R L; Pulyanina, Polina Y.; Nieden, Nicole I. zur

doi:10.1016/j.stemcr.2016.06.006

Cited by 62 publications

(70 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We next considered the impact of DAC treatment on gene expression. CDKN1A and CDKN1B are targeted by FOXO3A [ 30 ] and are downregulated in a variety of tumors. As shown in Figure 2(c) , protein expression of both of these genes was rare in untreated SKM-1 cells, but increased after DAC treatment, especially CDKN1A ( P < 0.01).…”

Section: Resultsmentioning

confidence: 99%

Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation

Zeng

Dai

Yan

et al. 2017

Journal of Immunology Research

View full text Add to dashboard Cite

The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment. We found that FOXO3A exists in an inactive, hyperphosphorylated form in SKM-1 cells, but that DAC both induces FOXO3A expression and reactivates the protein by reducing its phosphorylation level. Furthermore, we show that this FOXO3A activation is responsible for the DAC-induced differentiation of SKM-1 cells into monocytes, as well as for SKM-1 cell cycle arrest, apoptosis, and autophagy. Collectively, these results suggest that FOXO3A reactivation may contribute to the therapeutic effects of DAC in MDS.

show abstract

Section: Resultsmentioning

confidence: 99%

Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation

Zeng

Dai

Yan

et al. 2017

Journal of Immunology Research

View full text Add to dashboard Cite

show abstract

“…FOXO3a is a central transcription factor that mediates multiple physiological and pathological processes by inducing transcription of target genes involved in apoptosis [ 62 ], proliferation [ 63 ], cell cycle progression [ 64 ], survival [ 65 ] and DNA damage [ 66 ] (Fig. 2 ).…”

Section: Overview: Structure Regulation and Function Of Foxo3amentioning

confidence: 99%

Critical role of FOXO3a in carcinogenesis

et al. 2018

View full text Add to dashboard Cite

FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein–protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.

show abstract

“…Previous reports investigating the effects of high glucose on stem cell functions are controversial as there are differing perspectives. For example, some studies have shown that high glucose induces senescence and apoptosis in stem cells [1, 4, 5]. Conversely, other studies have shown that high glucose stimulates proliferation and enhances osteogenic differentiation potential in mesenchymal stem cells (MSCs) [6].…”

Section: Introductionmentioning

confidence: 99%

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

Choi

Lee

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) migration, and analyze the mechanism accompanied by this effect. Methods: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. Results: High concentration glucose (25 mM) elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS) promotes two signaling; JNK which regulates γ–secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. Conclusion: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.

show abstract

Glucose-Induced Oxidative Stress Reduces Proliferation in Embryonic Stem Cells via FOXO3A/β-Catenin-Dependent Transcription of p21cip1

Cited by 62 publications

References 44 publications

Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation

Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation

Critical role of FOXO3a in carcinogenesis

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

Contact Info

Product

Resources

About