The PI3K/AKT Signaling Pathway Controls the Quiescence of the Low-Rhodamine123-Retention Cell Compartment Enriched for Melanoma Stem Cell Activity

Stem Cells ◽  
2013 ◽  
Vol 31 (4) ◽  
pp. 641-651 ◽  
Author(s):  
Yasmine Touil ◽  
Thomas Zuliani ◽  
Isabelle Wolowczuk ◽  
Klaudia Kuranda ◽  
Jirina Prochazkova ◽  
...  
Keyword(s):  
Stem Cell ◽  
Signaling Pathway ◽  
Cell Activity ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Cell Compartment ◽  
Stem Cell Activity

Akt-Mediated Phosphorylation of Bmi1 Regulates Its Chromatin Association and Growth Promoting Properties.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3605-3605
Author(s):  
Yan Liu ◽  
Fan Liu ◽  
Xinyang Zhao ◽  
Goro Sashida ◽  
Anthony Deblasio ◽  
...  
Keyword(s):  
Stem Cell ◽  
Signaling Pathway ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Akt Signaling ◽  
Polycomb Group ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Self Renewal ◽  
Hematopoietic Stem

Abstract Abstract 3605 Poster Board III-541 The Polycomb group (PcG) protein Bmi1 maintains silencing of the Ink4a-Arf locus and plays a key role in stem cell self-renewal and oncogenesis. The phosphoinositide 3-kinase-Akt (PI3K-Akt) signaling pathway regulates cell survival, growth, metabolism, migration and angiogenesis. In response to acute Pten loss (which results in Akt activation), mouse embryonic fibroblasts (mefs) accumulate p16Ink4a and p19Arf and undergo senescence. Similarly, Bmi1 −/− mefs undergo premature senescence and accumulate p16Ink4a and p19Arf. PTEN and Bmi1 have similar effects on hematopoiesis; Pten deletion promotes hematopoietic stem cell (HSC) proliferation, resulting in HSC depletion, whereas loss of Bmi1 impairs HSC self-renewal capability, also leading to bone marrow failure. These similarities led us to examine whether the PI3K/Akt pathway functions upstream of Bmi1 to negatively regulate its function and indeed we found that PKB/Akt phosphorylates Bmi1 in vivo, which results in its dissociation from chromatin and in de-repression of the Ink4a-Arf locus. Furthermore, activation of the PI3K/Akt pathway suppresses the ability of Bmi1 to promote cell growth and tumourigenesis and decreases the global level of histone H2A ubiquitination. PI3K/Akt signaling is not active in hematopoietic stem cells, but it is active in more committed progenitor cells. Thus, phosphorylation and inactivation of Bmi1 by Akt may limit HSC self-renewal. Our study also provides a mechanism for the upregulation of p16Ink4a and p19Arf seen in cancer cells that have activation of the PI3K/Akt signaling pathway, and identifies important crosstalk between phosphorylation and chromatin structure. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MiR-223 Regulates Human Embryonic Stem Cell Differentiation by Targeting the IGF-1R/Akt Signaling Pathway

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e78769 ◽  
Author(s):  
Yan-Hui Yu ◽  
Li Zhang ◽  
Deng-Shu Wu ◽  
Zheng Zhang ◽  
Fang-Fang Huang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Signaling Pathway ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Akt Signaling ◽  
Embryonic Stem Cell Differentiation ◽  
Akt Signaling Pathway

scholarly journals Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

2020 ◽  
Author(s):  
Xu Yan ◽  
Yong Cao ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Umbilical Vein ◽  
Motor Evoked Potential ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Cord Injury

Abstract Background: Spinal cord injury (SCI) is a devastating clinical diseasewithout effectivetherapeuticapproach recently. In this study, we aim to investigate the effect of locally injection with exosome derived human urine stem cell (USC) embedding with hydrogelcould improve the spinal cord functional recovery after injury and the underlying mechanism.Methods:Exosome were isolate from USC andidentified by transmission electron microscopy and western blot. Functional assays using human umbilical vein endothelial cell (HUVEC) in vitro were performed to assess the effects of USC-Exosdeliverythe angiopoietin-like protein 3 (ANGPTL3) on tube formation and migration as well as their regulatory role in the PI3K/AKT signaling pathway activation. In vivo experiment we locally injection with exosome derived USC embedding with hydrogel for treatment of SCI. The effects of USC-Exos on functional recovery in spinal cord injury mice were tested by measuring motor evoked potential, histological and neovascular numbers. Meanwhile, the role of the candidate protein ANGPTL3 in USC-Exo for promoting angiogenesisin SCI was assessed.Results:In current study, we demonstrate that when given locallyinjection with exosomederivedhuman urine stem cell (USC) embeddingwith hydrogelcould pass the spinal cord blood brain barrier and delivery the angiopoietin-like protein 3 (ANGPTL3) to the injured spinal cord region. In addition, the administration of exosome derived from human USC could enhance spinal cord neurological functional recovery by promoting angiogenesis.The mechanism studies revealed that ANGPTL3 are enriched in USCexosome(USC-Exo) and required for USC exosome promoting angiogenesis. Functional studies further confirmed the effects caused by exosome derived from USC on angiogenesis wasmediated by PI3K/AKT signaling pathway. Conclusion:Collectively, our results indicated that USC derived exosome serve as a critical regulator of angiogenesis by transferring ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals LncRNA MALAT1 Promotes Cancer Metastasis in Osteosarcoma via Activation of the PI3K-Akt Signaling Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1313-1326 ◽  
Author(s):  
Yong  Chen ◽  
Wending Huang ◽  
Wei Sun ◽  
Biqiang Zheng ◽  
Chunmeng Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Cancer Metastasis ◽  
Soft Tissues ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Akt Signaling Pathway

Background/Aims: LncRNAs have been reported to be vital regulators of the progression of osteosarcoma, although the underlying mechanisms are not completely understood. Methods: The levels of MALAT1 and miR-129-5p expression were measured using qRT-PCR. Cell growth was determined using the CCK-8 and colony formation assays. Cell migration and invasion were detected using the wound healing and Transwell invasion assays, respectively. Tumor growth was determined with a xenograft model. Results: MALAT1 was significantly up-regulated in osteosarcoma tissues compared with adjacent non-tumor soft tissues. Overexpression of MALAT1 promoted osteosarcoma cell proliferation, migration, and invasion in vitro and enhanced tumor growth in a tumor xenograft mouse model. MALAT1 promoted osteosarcoma progression by modulating stem cell-like properties. Moreover, rescue experiment and luciferase reporter assay results indicated that MALAT1 modulates RET expression by sponging miR-129-5p in osteosarcomas. Furthermore, MALAT1 augmented the expression of downstream proteins of the RET-Akt pathway. MALAT1 was consistently significantly increased in osteosarcoma tissues and MALAT1 expression was positively correlated with tumor size and metastasis. High expression of MALAT1 was significantly associated with poor outcomes in patients with osteosarcomas. MALAT1 expression was positively related to RET and negatively related to miR-129-5p in osteosarcoma samples and xenograft tumors. MALAT1 functioned as an oncogenic lncRNA in osteosarcomas and was as an independent prognostic indicator. Conclusion: Our data revealed for the first time that MALAT1 increases stem cell-like properties by up-regulating RET via sponging miR-129-5p, and thus activates the PI3K-Akt signaling pathway and provides potential therapeutic targets for osteosarcoma treatment.

scholarly journals Zinc L-Aspartate enhances intestinal stem cell activity to protect the integrity of the intestinal mucosa against deoxynivalenol through activation of the Wnt/β-catenin signaling pathway

2020 ◽  
Vol 262 ◽  
pp. 114290 ◽  
Author(s):  
Jia-yi Zhou ◽  
Hua-lin Lin ◽  
Zhe Wang ◽  
Sai-wu Zhang ◽  
Deng-gui Huang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Signaling Pathway ◽  
Intestinal Mucosa ◽  
Cell Activity ◽  
Intestinal Stem Cell ◽  
Stem Cell Activity
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