Pharmacological Notch pathway inhibition leads to cell cycle arrest and stimulates ascl1 and neurogenin2 genes expression in dental pulp stem cells-derived neurospheres

2019 ◽  
Vol 41 (6-7) ◽  
pp. 873-887 ◽  
Author(s):  
Ali Niapour ◽  
Hatef Ghasemi Hamidabadi ◽  
Nazila Niapour ◽  
Perham Mohammadi ◽  
Marzieh Sharifi Pasandi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Cycle Arrest ◽  
Dental Pulp ◽  
Notch Pathway ◽  
Dental Pulp Stem Cells ◽  
Cycle Arrest ◽  
Genes Expression ◽  
Pathway Inhibition

Irradiation of Adult Human Dental Pulp Stem Cells Provokes Activation of p53, Cell Cycle Arrest, and Senescence but Not Apoptosis

2010 ◽  
Vol 19 (12) ◽  
pp. 1855-1862 ◽  
Author(s):  
Darina Muthna ◽  
Tomas Soukup ◽  
Jirina Vavrova ◽  
Jaroslav Mokry ◽  
Jana Cmielova ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Cycle Arrest ◽  
Dental Pulp ◽  
Dental Pulp Stem Cells ◽  
Adult Human ◽  
Cycle Arrest ◽  
Human Dental Pulp

scholarly journals PAWI-2 overcomes tumor stemness and drug resistance via cell cycle arrest in integrin β3-KRAS-dependent pancreatic cancer stem cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiongjia Cheng ◽  
John R. Cashman
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Cycle Arrest ◽  
Specific Inhibitor ◽  
Feedback Mechanism ◽  
Major Health Problem ◽  
Cycle Arrest ◽  
Drug Inhibition

Abstract Today, pancreatic cancer (PC) remains a major health problem in the US. The fact that cancer stem cells (CSCs) become enriched in humans following anti-cancer therapy implicates CSCs as key contributors to tumor dormancy, metastasis, and relapse in PC. A highly validated CSC model (FGβ3 cells) was used to test a novel compound (PAWI-2) to eradicate CSCs. Compared to parental bulk FG cells, PAWI-2 showed greater potency to inhibit cell viability and self-renewal capacity of FGβ3 cells. For FGβ3 cells, dysregulated integrin β3-KRAS signaling drives tumor progression. PAWI-2 inhibited β3-KRAS signaling independent of KRAS. This is clinically relevant. PAWI-2 targeted the downstream TBK1 phosphorylation cascade that was negatively regulated by optineurin phosphorylation via a feedback mechanism. This was confirmed by TBK1 genetic knockdown or co-treatment with TBK1-specific inhibitor (MRT67307). PAWI-2 also overcame erlotinib (an EGFR inhibitor) resistance in FGβ3 cells more potently than bortezomib. In the proposed working model, optineurin acts as a key regulator to link inhibition of KRAS signaling and cell cycle arrest (G2/M). The findings show PAWI-2 is a new approach to reverse tumor stemness that resensitizes CSC tumors to drug inhibition.

scholarly journals METTL3-mediated M6a Modification Regulates Cell Cycle Progression of Dental Pulp Stem Cells

2021 ◽  
Author(s):  
Haiyun Luo ◽  
Wenjing Liu ◽  
Yanli Zhang ◽  
Xiao Jiang ◽  
Shiqing Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Differentially Expressed Genes ◽  
Dental Pulp ◽  
Cell Cycle Control ◽  
Dental Pulp Stem Cells ◽  
Differentially Expressed ◽  
Expression Level

Abstract Background: Dental pulp stem cells (DPSCs) exhibited self-renewal, pluripotency capacity and served as promising cells source in endodontic regeneration and tissue engineering. Meanwhile, the regenerative capacity of DPSCs is limited and reduced in long lifespan. N6-methyladenosine (m6A) is the most prevalent, reversible internal modification in RNAs. The methyltransferases complex and demethylases mediated m6A methylation and cooperated to impact various biological processes associated with stem cell fate determination. However, the biological effect of m6A methylation in DPSCs remained unclear. Methods: Cell surface markers and differentiation potential of primary DPSCs were identified and m6A immunoprecipitation with deep sequencing (m6A RIP-seq) was used to uncover characteristics of m6A modifications in DPSCs transcriptome. Expression level of m6A-related genes were evaluated in immature/mature pulp tissues and cells. Lentiviral vectors were constructed to knockdown or overexpress methyltransferase like 3 (METTL3). Cell morphology, viability, senescence and apoptosis were further analyzed by β-galactosidase, TUNEL staining and flow cytometry. Bioinformatic analysis combing m6A RIP and shMETTL3 RNA-seq was used to functionally enrich overlapped genes and screen target of METTL3. Cell cycle distributions were assayed by flow cytometry and m6A RIP-qPCR was used to confirm METTL3 mediated m6A methylation in DPSCs. Results: Here, m6A peaks distribution, binding area and motif in DPSCs were first revealed by m6A RIP-seq. We also found a relative high expression level of METTL3 in immature DPSCs with superior regenerative potential and METTL3 knockdown induced cell apoptosis and senescence. Furthermore, Conjoint analysis of m6A RIP and RNA-sequencing showed differentially expressed genes affected by METTL3 depletion was mainly enriched in cell cycle, mitosis and alteration of METTL3 expression resulted in cell cycle arrest which indicated METTL3 make essential effect in cell cycle control. To further investigate underlying mechanisms, we explored proteins interaction network of differentially expressed genes and Polo-like Kinase 1 (PLK1), a critical cycle modulator was identified as target of METTL3-mediated m6A methylation in DPSCs. Conclusions: These results revealed m6A methylated hallmarks in DPSCs and a regulatory role of METTL3 in cell cycle control. Our study shed light on therapeutic approaches in vital pulp therapy and serve new insight in stem cells based tissue engineering.

scholarly journals Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest

2017 ◽  
Vol 21 (1) ◽  
pp. 107-119.e6 ◽  
Author(s):  
Phong Dang Nguyen ◽  
David Baruch Gurevich ◽  
Carmen Sonntag ◽  
Lucy Hersey ◽  
Sara Alaei ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Cycle Arrest ◽  
Tissue Growth ◽  
Muscle Stem Cells ◽  
Cycle Arrest ◽  
G2 Cell Cycle Arrest

The increase in BIK expression following ERK1/2 pathway inhibition is a consequence of G1 cell-cycle arrest and not a direct effect on BIK protein stability

2014 ◽  
Vol 459 (3) ◽  
pp. 513-524 ◽  
Author(s):  
Matthew J. Sale ◽  
Simon J. Cook
Keyword(s):  
Cell Cycle ◽  
Protein Stability ◽  
Cell Cycle Arrest ◽  
Direct Effect ◽  
Cycle Arrest ◽  
Apoptotic Protein ◽  
G1 Cell Cycle Arrest ◽  
Pathway Inhibition

In contrast with BIMEL, the increase in expression of the pro-apoptotic protein BIK following inhibition of ERK1/2 signalling is likely to be a consequence of G1 cell-cycle arrest and not a direct effect on BIK protein stability.

scholarly journals Sphingosine kinases protect murine embryonic stem cells from sphingosine-induced cell cycle arrest

Stem Cells ◽  
2020 ◽  
Vol 38 (5) ◽  
pp. 613-623
Author(s):  
Suveg Pandey ◽  
Kelly M. Banks ◽  
Ritu Kumar ◽  
Andrew Kuo ◽  
Duancheng Wen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Cycle Arrest ◽  
Embryonic Stem ◽  
Murine Embryonic Stem Cells ◽  
Cycle Arrest ◽  
Sphingosine Kinases

scholarly journals Resveratrol Induces Cell Cycle Arrest and Apoptosis in Malignant NK Cells via JAK2/STAT3 Pathway Inhibition

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55183 ◽  
Author(s):  
Ly Quoc Trung ◽  
J. Luis Espinoza ◽  
Akiyoshi Takami ◽  
Shinji Nakao
Keyword(s):  
Cell Cycle ◽  
Nk Cells ◽  
Cell Cycle Arrest ◽  
Stat3 Pathway ◽  
Cycle Arrest ◽  
Pathway Inhibition
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