WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells

Zhang, Kai; Guo, Yanjing; Wang, Xue; Zhao, Huifang; Ji, Zhongzhong; Cheng, Chung–Ying; Li, Li; Fang, Yuxiang; Xu, Dawei; Zhu, Helen He; Gao, Wei‐Qiang

doi:10.1158/0008-5472.can-16-1887

Cited by 121 publications

(90 citation statements)

References 45 publications

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“…138,139 GSK3 genes are critical for β-catenin regulation; therefore, many researchers expect the occurrence of GSK3 mutations, but GSK3 mutations are not correlated with cancer occurrence. In addition, some genes (pyruvate kinase isozyme M2 (PKM2) in breast cancer 140 and telomerase reverse transcriptase (TERT) in prostate cancer 141 ) and microRNAs (miR-164a in colorectal cancer 142 and miR-582-3p in non-small-cell lung cancer 143 ) inhibit the activity of APC, Axin, and GSK3β to promote the accumulation of β-catenin in the cytoplasm.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

“…Some proteins (DKK2 (Dickkopf-related protein 2), DACT1, CDH11, GECG, PKM2, EZH2, CD44v6, MYC, and TERT), microRNAs (miR-1246, miR-9, miR-92a, miR-544a, and miR-483-5p), and long noncoding RNAs (lncR-β-catm and lncR-TCF7) regulate the activation of the Wnt/β-catenin pathway in CSCs prostate CSCs. 141 Capillary morphogenesis gene 2 increases the expression of nuclear β-catenin to regulate the self-renewal and tumorigenicity of gastric CSCs, 151 and SMYD3, which is located downstream of the Wnt pathway, has a similar effect. 152 In addition, long noncoding RNAs and microRNAs also promote selfrenewal of CSCs through the Wnt signaling pathway.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

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Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

View full text Add to dashboard Cite

show abstract

“…Over the last decades, different strategies have been suggested for eradicating PCSCs that are resistance to conventional therapeutic agents. One of these strategies is targeting the signaling pathways that regulate the maintenance and survival of PCSCs such as WNT/β-catenin and PI3K/ AKT [164][165][166]. Inhibition of these signaling routes results in the sensitization of the experimental tumor models to the different types of therapy [164,[167][168][169].…”

Section: Genetic Evolvingmentioning

confidence: 99%

Concise Review: Prostate Cancer Stem Cells: Current Understanding

et al. 2018

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Prostate cancer (PCa) is heterogeneous, harboring phenotypically diverse cancer cell types. PCa cell heterogeneity is caused by genomic instability that leads to the clonal competition and evolution of the cancer genome and by epigenetic mechanisms that result in subclonal cellular differentiation. The process of tumor cell differentiation is initiated from a population of prostate cancer stem cells (PCSCs) that possess many phenotypic and functional properties of normal stem cells. Since the initial reports on PCSCs in 2005, there has been much effort to elucidate their biological properties, including unique metabolic characteristics. In this Review, we discuss the current methods for PCSC enrichment and analysis, the hallmarks of PCSC metabolism, and the role of PCSCs in tumor progression. Stem Cells 2018;36:1457-1474.

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“…Wnt/β-catenin signaling is associated with CSC properties. Activation of Wnt/β-catenin signaling orchestrates the self-renewal of CSCs and induces several stemness factors, such as OCT4, SOX2, and CD44 [114,115]. Members of the secreted frizzled-related protein (SFRP) family are Wnt antagonists and inactivate Wnt ligands, impairing signaling pathways from FZD receptors and low-density lipoprotein receptor-related proteins (LRPs) [114].…”

Section: Wnt/β-catenin Signaling and Cscsmentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells

Cited by 121 publications

References 45 publications

Targeting cancer stem cell pathways for cancer therapy

Targeting cancer stem cell pathways for cancer therapy

Concise Review: Prostate Cancer Stem Cells: Current Understanding

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

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