The phosphoinositide-3-kinase/Akt pathway mediates the transient increase in Nanog expression during differentiation of F9 cells

Kim, Jung Sun; Kim, Byung Soo; Kim, Jiha; Park, Choon-Sik; Chung, Il Yup

doi:10.1007/s12272-010-0719-y

Cited by 27 publications

(29 citation statements)

References 29 publications

(43 reference statements)

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“…Although RA was previously described as an inducer of differentiation, its presence promotes AKT-dependent phosphorylation of the chromatin remodeler SATB1, which binds to SOX2 thereby preventing it from associating with Oct4 to maintain pluripotency. In addition, and contrary to what was described earlier [186], active AKT signaling in P19 cells induces a transient increase in Nanog expression [187], which seems counterintuitive because AKT inhibits pluripotency markers. However, it is more complex than this as Oct4 in ECCs can bind to the human AKT1 promoter, and this is dependent on its phosphorylation state controlled by AKT itself [188].…”

Section: Pluripotency Factors and Signaling Crosstalkcontrasting

confidence: 81%

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Kelly

Gatie

2017

Stem Cells International

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Just over ten years have passed since the seminal Takahashi-Yamanaka paper, and while most attention nowadays is on induced, embryonic, and cancer stem cells, much of the pioneering work arose from studies with embryonal carcinoma cells (ECCs) derived from teratocarcinomas. This original work was broad in scope, but eventually led the way for us to focus on the components involved in the gene regulation of stemness and differentiation. As the name implies, ECCs are malignant in nature, yet maintain the ability to differentiate into the 3 germ layers and extraembryonic tissues, as well as behave normally when reintroduced into a healthy blastocyst. Retinoic acid signaling has been thoroughly interrogated in ECCs, especially in the F9 and P19 murine cell models, and while we have touched on this aspect, this review purposely highlights how some key transcription factors regulate pluripotency and cell stemness prior to this signaling. Another major focus is on the epigenetic regulation of ECCs and stem cells, and, towards that end, this review closes on what we see as a new frontier in combating aging and human disease, namely, how cellular metabolism shapes the epigenetic landscape and hence the pluripotency of all stem cells.

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Section: Pluripotency Factors and Signaling Crosstalkcontrasting

confidence: 81%

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Kelly

Gatie

2017

Stem Cells International

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“…The expression of Nanog, the second most important pluripotent gene, can be positively regulated by RA, as has been shown in some recent studies [77, 86]. In this case, Nanog expression is probably induced through the induction of insulin-like growth factor (IGF) expression by RA or other retinoids [86]. IGF is a strong inductor of the PI3-K pathway, whose activity leads to the increasing expression of Nanog in ES cells [87, 88].…”

Section: Alkaline Phosphatase and Stem Cellsmentioning

confidence: 72%

“…However, the expression of Oct-4 is directly inhibited by RA [85]. The expression of Nanog, the second most important pluripotent gene, can be positively regulated by RA, as has been shown in some recent studies [77, 86]. In this case, Nanog expression is probably induced through the induction of insulin-like growth factor (IGF) expression by RA or other retinoids [86].…”

Section: Alkaline Phosphatase and Stem Cellsmentioning

confidence: 99%

Alkaline Phosphatase in Stem Cells

Štefková

Procházková

Pachernı́k

2015

Stem Cells International

161

109

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Alkaline phosphatase is an enzyme commonly expressed in almost all living organisms. In humans and other mammals, determinations of the expression and activity of alkaline phosphatase have frequently been used for cell determination in developmental studies and/or within clinical trials. Alkaline phosphatase also seems to be one of the key markers in the identification of pluripotent embryonic stem as well as related cells. However, alkaline phosphatases exist in some isoenzymes and isoforms, which have tissue specific expressions and functions. Here, the role of alkaline phosphatase as a stem cell marker is discussed in detail. First, we briefly summarize contemporary knowledge of mammalian alkaline phosphatases in general. Second, we focus on the known facts of its role in and potential significance for the identification of stem cells.

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“…Whether ATRA increases or decreases PI3K activity appears to vary with cell type. For example, in differentiating F9 and glial cells, ATRA increases PI3K activity (33,34). With respect to cancer cells, ATRA has been shown to induce PI3K activity in MCF-7 breast cancer cells (15).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol 3-Kinase Mediates the Ability of Retinol to Decrease Colorectal Cancer Cell Invasion

Lengyel

Park

Brunson

et al. 2014

Nutrition and Cancer

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Previously, we showed that retinol (vitamin A) decreased both colorectal cancer cell invasion and phosphatidylinositol 3-kinase (PI3K) activity through a retinoic acid receptor-independent mechanism. Here, we determined if these phenomena were related by using parental HCT-116 cells that harbor 1 allele of wild-type PI3K and 1 allele of constitutively active (ca) PI3K and 2 mutant HCT-116 cell lines homozygous for caPI3K. In vitro, treatment of parental HCT-116 cells with 10 μM retinol reduced cell invasion whereas treatment of mutant HCT-116 cell lines with retinol did not. Treatment with 10 μM retinol also decreased the activity of matrixmetalloproteinase-9 and increased tissue inhibitor of matrixmetalloproteinase-I levels in parental, but not mutant, HCT-116 cells. Finally, parental or mutant cells were intrasplenically injected into athymic mice consuming diets with or without supplemental vitamin A. As expected, vitamin A supplementation tended (P = 0.18) to reduce the incidence of metastases in mice injected with the parental cell line and consuming the supplemented diet. In contrast, metastatic incidence was not affected (P = 1.00) by vitamin A supplementation in mice injected with mutant cells. These data indicate that the capacity of retinol to inhibit PI3K activity confers its ability to decrease colorectal cancer metastasis.

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The phosphoinositide-3-kinase/Akt pathway mediates the transient increase in Nanog expression during differentiation of F9 cells

Cited by 27 publications

References 29 publications

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Mechanisms Regulating Stemness and Differentiation in Embryonal Carcinoma Cells

Alkaline Phosphatase in Stem Cells

Phosphatidylinositol 3-Kinase Mediates the Ability of Retinol to Decrease Colorectal Cancer Cell Invasion

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