Pdcd4 restrains the self-renewal and white-to-beige transdifferentiation of adipose-derived stem cells

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

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Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200512105347 ◽

2020 ◽

Vol 15 (6) ◽

pp. 531-546 ◽

Cited By ~ 1

Author(s):

Hwa-Yong Lee ◽

In-Sun Hong

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Oxidative Phosphorylation ◽

Metabolic Pathways ◽

Critical Role ◽

The Self ◽

Specific Cell ◽

Differentiation Potential ◽

Self Renewal ◽

Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

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Propofol Inhibits the Proliferation, Migration, and Stem-like Properties of Bladder Cancer Mainly by Suppressing the Hedgehog Pathway

Cell Transplantation ◽

10.1177/0963689720985113 ◽

2021 ◽

Vol 30 ◽

pp. 096368972098511

Author(s):

Gang Li ◽

Xu Zhang ◽

Xiangyang Guo ◽

Yi Li ◽

Chong Li

Keyword(s):

Stem Cells ◽

Bladder Cancer ◽

Bladder Tumor ◽

Therapeutic Agent ◽

Tumor Formation ◽

The Self ◽

Hedgehog Pathway ◽

Self Renewal ◽

Intravenous Anesthetic ◽

Novel Therapeutic

Bladder cancer is one of the most common malignancies. The existence of bladder cancer stem cells (BCSCs) has been suggested to underlie bladder tumor initiation and recurrence. Propofol is a commonly used intravenous anesthetic. Here, we find that propofol can dramatically block the activation of Hedgehog pathway in BCSCs. The propofol strongly repressed the growth of cancer cells. Attenuated proliferation and enhanced apoptosis of tumor cells were observed upon propofol stimulation. Furthermore, propofol reduced the self-renewal ability of BCSCs as well as the tumor formation. In conclusion, propofol is potentially used as a novel therapeutic agent for bladder cancer by targeting self-renewal through inhibiting Hedgehog pathway.

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Musashi2 Is Required for the Self-Renewal and Pluripotency of Embryonic Stem Cells

PLoS ONE ◽

10.1371/journal.pone.0034827 ◽

2012 ◽

Vol 7 (4) ◽

pp. e34827 ◽

Cited By ~ 28

Author(s):

Erin L. Wuebben ◽

Sunil K. Mallanna ◽

Jesse L. Cox ◽

Angie Rizzino

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

The Self ◽

Self Renewal

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3065 – ETV6-RUNX1 ENHANCES THE SELF-RENEWAL OF HEMATOPOIETIC STEM CELLS AND CORRUPTS EARLY LYMPHOID DIFFERENTIATION

Experimental Hematology ◽

10.1016/j.exphem.2020.09.082 ◽

2020 ◽

Vol 88 ◽

pp. S58

Author(s):

Mohamed Eldeeb ◽

Jonas Ungerbäck ◽

Mikael Sigvardsson ◽

David Bryder

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

The Self ◽

Self Renewal ◽

Hematopoietic Stem

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Comprehensive Identification of Krüppel-Like Factor Family Members Contributing to the Self-Renewal of Mouse Embryonic Stem Cells and Cellular Reprogramming

PLoS ONE ◽

10.1371/journal.pone.0150715 ◽

2016 ◽

Vol 11 (3) ◽

pp. e0150715 ◽

Cited By ~ 15

Author(s):

Hyojung Jeon ◽

Tsuyoshi Waku ◽

Takuya Azami ◽

Le Tran Phuc Khoa ◽

Jun Yanagisawa ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Family Members ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Cellular Reprogramming ◽

The Self ◽

Self Renewal

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Inhibition of β‑catenin protein expression by triptolide affects self-renewal of liver cancer stem cells

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.23016 ◽

2015 ◽

Vol 10 (2) ◽

pp. 455 ◽

Cited By ~ 1

Author(s):

Jian-Bo Zhou ◽

Gang Peng ◽

Yu-Cheng Jia ◽

Jun Li ◽

Jia Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Cancer Stem Cells ◽

Liver Cancer ◽

Inhibitory Concentration ◽

The Self ◽

Tripterygium Wilfordii ◽

Self Renewal ◽

Liver Cancer Stem Cells ◽

Novel Agent

<p>The present study demonstrates the effects of triptolide, one of the constituents from Tripterygium wilfordii, on the self‑renewal capacity of human hepatocellular carcinoma. The investigation revealed that triptolide markedly prevented the proliferation of liver cancer stem cells (LCSCs). For the LCSCs the minimum inhibitory concentration of triptolide was 0.6 μM. There was a significant and obvious decrease in the capacity of LCSCs to form self-sphere. Furthermore, triptolide reduced the sphere-forming capacity of LCSCs along with inhibition of β‑catenin expression. However, the exposure of triptolide-treated cells to lithium chloride, an activator the Wnt/β-catenin signaling pathway, reversed the triptolide-induced inhibition of β-catenin expression and inhibited the self-renewal capacity. Therefore, triptolide effectively eradicates LCSCs through the inhibition of β-catenin protein and may act as a novel agent for the treatment of hepatocellular carcinoma.</p><p> </p>

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Both Gfrα1a and Gfrα1b Are Involved in the Self-Renewal and Maintenance of Spermatogonial Stem Cells in Medaka

Stem Cells and Development ◽

10.1089/scd.2018.0177 ◽

2018 ◽

Vol 27 (23) ◽

pp. 1658-1670

Author(s):

Yang Zhao ◽

Zhuo Yang ◽

Yuan Wang ◽

Yubing Luo ◽

Fan Da ◽

...

Keyword(s):

Stem Cells ◽

Spermatogonial Stem Cells ◽

The Self ◽

Self Renewal

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Anlotinib Induced Apoptosis and Regulated the Chemosensitivity and Immune-Related Properties of Leukemia Stem Cells By Inhibiting JAK2-STAT3/5 Signaling

Blood ◽

10.1182/blood-2020-139179 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 12-12

Author(s):

Long Liu ◽

Long Yue Jiang ◽

Bing Xu

Keyword(s):

Stem Cells ◽

Tyrosine Kinase ◽

Immune Evasion ◽

Tyrosine Kinases ◽

Receptor Expression ◽

The Self ◽

Leukemia Stem Cells ◽

Self Renewal ◽

Stat Signaling ◽

Apoptotic Proteins

Acute myeloid leukemia (AML) is derived from small populations of leukemia stem cells (LSCs) characterized by the self-renewal and chemoresistant properties. Residual LSCs after chemotherapy remain as the critical barriers to cure. Clearance of LSCs might rationally lead to an improvement of clinical outcome. Recently studies showed that JAK/STAT signaling play an important role in the self-renewal of AML-LSCs due to increased growth factor (GF) receptor expression such as c-kit, FLT3, CD123 and altered GF signaling by activating tyrosine kinases. Therefore, targeting such tyrosine kinases might be a strategy to eliminate LSCs. Anlotinib displayed its anti-tumor activity in lung cancer by targeting tyrosine kinase of VEGFR, FGFR, PDGFR and c-kit. However, whether anlotinib could inhibit the GF receptor-related tyrosine kinase overactivation and its downstream JAK-STAT signaling, and subsequently kill LSCs or regulate LSCs biology remains largely unknown. To explore whether anlotinib could exert effective ani-LSCs activity, we treated LSC like cell lines (CD34+CD38-KG-1 and Kasumi-1) with anlotinib, and found anlotinib could effectively induce apoptosis of LSC-like cells in a dose- and time-dependent manner. Similar results were observed in primary CD34+CD38-AML LSCs; notably, anlotinib did not significantly kill normal CD34+ cells in vitro. Additionally, the anti-LSC activity of anlotinib was further confirmed in the xenograft mouse model by injection of Kasumi cells (LSC-like cell line) into irradiated female BALB/c nude mice. To determine whether anlotinib could inhibit the over activation of the GF receptor-related tyrosine kinase, we performed western blot at 12h after anlotinib treatment when LSC-like cells did not showed significant apoptosis. As a result, anlotinib inhibit c-kit phosphorylation and JAK2 activation. Intriguingly, unlike JAK2 inhibitors, anlotinib could not only the inhibit phosphorylation of STAT3 and STAT5 but also downregulate their expression. Chemoresistance and immune evasion were the key features of LSCs, JAK2-STAT3/5 signaling was reported to involved in chemoresistance by upregulating anti-apoptotic proteins such as Bcl-2 ,Mcl-1 and also involved in immune escape by inducing immune suppressive molecules such as PD-L1 ,TGF-β.Thus we evaluated Bcl-2 expression and found a significant decrease in LSC-likes cells after anlotinib treatment. Similarly, PD-L1 and TGF-β were also significantly downregulated after anlotinib treatment. In conclusion, anlotinib not only displayed the effective anti-LSCs activity but also might regulate the chemoresistance and immune evasion of LSC by downregulating the anti-apoptotic proteins and suppressive molecules such as PD-L1, TGF-β respectively. Consequently, anlotinib might has the potential to contribute to a deeper clearance of LSCs by combining with chemotherapy or immunotherapy. Disclosures No relevant conflicts of interest to declare.

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Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells

Experimental & Molecular Medicine ◽

10.1038/s12276-019-0328-x ◽

2019 ◽

Vol 51 (11) ◽

pp. 1-20 ◽

Cited By ~ 2

Author(s):

Jun-Cheng Guo ◽

Yi-Jun Yang ◽

Jin-Fang Zheng ◽

Jian-Quan Zhang ◽

Min Guo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Stem Cells ◽

Stem Cell ◽

Wnt Signaling ◽

Signaling Pathway ◽

Methylation Level ◽

Wnt Signaling Pathway ◽

The Self ◽

Self Renewal

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

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