scholarly journals Targeting Signaling Pathways in Cancer Stem Cells for Cancer Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jeffrey Koury ◽  
Li Zhong ◽  
Jijun Hao
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Signaling Pathways ◽  
Small Subset ◽  
Self Renewal ◽  
Multiple Tumor ◽  
Notch Pathways ◽  
Tumor Types ◽  
Heterogeneous Tumor

The Wnt, Hedgehog, and Notch pathways are inherent signaling pathways in normal embryogenesis, development, and hemostasis. However, dysfunctions of these pathways are evident in multiple tumor types and malignancies. Specifically, aberrant activation of these pathways is implicated in modulation of cancer stem cells (CSCs), a small subset of cancer cells capable of self-renewal and differentiation into heterogeneous tumor cells. The CSCs are accountable for tumor initiation, growth, and recurrence. In this review, we focus on roles of Wnt, Hedgehog, and Notch pathways in CSCs’ stemness and functions and summarize therapeutic studies targeting these pathways to eliminate CSCs and improve overall cancer treatment outcomes.

scholarly journals Graphene oxide selectively targets cancer stem cells, across multiple tumor types: Implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”

Oncotarget ◽  
2015 ◽  
Vol 6 (6) ◽  
pp. 3553-3562 ◽  
Author(s):  
Marco Fiorillo ◽  
Andrea F. Verre ◽  
Maria Iliut ◽  
Maria Peiris-Pagés ◽  
Bela Ozsvari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Graphene Oxide ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Multiple Tumor ◽  
Tumor Types

scholarly journals Deubiquitinating Enzyme-Mediated Signaling Networks in Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3253
Author(s):  
Kamini Kaushal ◽  
Suresh Ramakrishna
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Deubiquitinating Enzymes ◽  
Self Renewal ◽  
Stem Cell Fate ◽  
Multiple Tumor ◽  
Cell Fate Decisions

Cancer stem cells (CSCs) have both the capacity for self-renewal and the potential to differentiate and contribute to multiple tumor properties, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Thus, CSCs are considered to be promising therapeutic targets for cancer therapy. The function of CSCs can be regulated by ubiquitination and deubiquitination of proteins related to the specific stemness of the cells executing various stem cell fate choices. To regulate the balance between ubiquitination and deubiquitination processes, the disassembly of ubiquitin chains from specific substrates by deubiquitinating enzymes (DUBs) is crucial. Several key developmental and signaling pathways have been shown to play essential roles in this regulation. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of CSCs. These signaling pathways have been experimentally shown to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. In this review, we focus on the DUBs involved in CSCs signaling pathways, which are vital in regulating their stem-cell fate determination.

scholarly journals Current Strategies for Identification of Glioma Stem Cells: Adequate or Unsatisfactory?

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Brescia ◽  
Cristina Richichi ◽  
Giuliana Pelicci
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Cell Phenotype ◽  
Multiple Tumor ◽  
Early Results ◽  
Tumorigenic Potential ◽  
Tumor Types

Cancer stem cells (CSCs) were isolated in multiple tumor types, including human glioblastomas, and although the presence of surface markers selectively expressed on CSCs can be used to isolate them, no marker/pattern of markers are sufficiently robust to definitively identify stem cells in tumors. Several markers were evaluated for their prognostic value with promising early results, however none of them was proven to be clinically useful in large-scale studies, leading to outstanding efforts to identify new markers. Given the heterogeneity of human glioblastomas further investigations are necessary to identify both cancer stem cell-specific markers and the molecular mechanisms sustaining the tumorigenic potential of these cells to develop tailored treatments. Markers for glioblastoma stem cells such as CD133, CD15, integrin-α6, L1CAM might be informative to identify these cells but cannot be conclusively linked to a stem cell phenotype. Overlap of expression, functional state and morphology of different subpopulations lead to carefully consider the techniques employed so far to isolate these cells. Due to a dearth of methods and markers reliably identifying the candidate cancer stem cells, the isolation/enrichment of cancer stem cells to be therapeutically targeted remains a major challenge.

scholarly journals Norcantharidin, Derivative of Cantharidin, for Cancer Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chen-Hsi Hsieh ◽  
K. S. Clifford Chao ◽  
Hui-Fen Liao ◽  
Yu-Jen Chen
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Treatment ◽  
Treatment Resistance ◽  
Notch Signaling Pathway ◽  
Chemotherapeutic Agents ◽  
Water Soluble ◽  
Self Renewal ◽  
Active Efflux ◽  
Effective Strategies

Cancer stem cells (CSCs) existing in human cancers have been demonstrated to be a major cause of cancer treatment resistance, invasion, metastasis, and relapse. Self-renewal pathways, Wnt/β-catenin, Sonic hedgehog (Shh), and the Notch signaling pathway play critical roles in developing CSCs and lead to angiogenesis, migration, invasion, and metastasis. Multidrug resistance (MDR) is an unfavorable factor causing the failure of treatments against cancer cells. The most important and thoroughly studied mechanism involved in MDR is the active efflux of chemotherapeutic agents through membrane drug transporters. There is growing evidence that Norcantharidin (NCTD), a water-soluble synthetic small molecule derivative of naturally occurring cantharidin from the medicinal insect blister beetle (Mylabris phalerataPallas), is capable of chemoprevention and tumor inhibition. We summarize investigations into the modulation of self-renewal pathways and MDR in CSCs by NCTD. This review may aid in further investigation of using NCTD to develop more effective strategies for cancer treatment to reduce resistance and recurrence.

scholarly journals Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease

Oncotarget ◽  
2015 ◽  
Vol 6 (7) ◽  
pp. 4569-4584 ◽  
Author(s):  
Rebecca Lamb ◽  
Bela Ozsvari ◽  
Camilla L. Lisanti ◽  
Herbert B. Tanowitz ◽  
Anthony Howell ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Multiple Tumor ◽  
Tumor Types

scholarly journals Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Thahomina Khan ◽  
Horacio Cabral
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Self Renewal ◽  
Tumor Relapse ◽  
Intracellular Signaling Pathways ◽  
Abnormal Glycosylation

Cancer stem cell (CSCs) are deemed as one of the main reasons of tumor relapse due to their resistance to standard therapies. Numerous intracellular signaling pathways along with extracellular features are crucial in regulating CSCs properties, such as heterogeneity, plasticity and differentiation. Aberrant glycosylation of these cellular signaling pathways and markers of CSCs have been directly correlated with maintaining survival, self-renewal and extravasation properties. In this review, we highlight the importance of glycosylation in promoting stemness character of CSCs, and present strategies for targeting abnormal glycosylation to eliminate the resistant CSC population.

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Polyhomeotic Homolog 3 and Sonic Hedgehog Signaling Pathways

2019 ◽  
Author(s):  
FanPing Wang ◽  
Jiateng Zhong ◽  
Shanshan Wang ◽  
Caijuan Qiao ◽  
Xiangyang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Background: Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. Methods: Lung cancer stem cells (CD133-positive cells) were isolated by MACs and then measured by flow cytometry. The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The expressions of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) in cells were measured by quantitative reverse transcription polymerase chain reaction (qPCR) and western blot assays. The expression of transcription factor SOX2 in lung cancer stem cells was also determined by western blot assay. Shh was knocked down by siRNA to further study the role of SFN and Shh signaling pathways in lung cancer. Results: SFN inhibited the proliferation of lung cancer cells and lung cancer stem cells simultaneously. Meanwhile, we observed that Sonic Hedgehog (SHH) signaling pathway, SOX2 and Polyhomeotic Homolog 3 (PHC3) were highly activated in lung cancer stem cells. Knock-down of Shh led to reduced H460 and A549 cells proliferation. Furthermore, we observed that SFN inhibited the activity of PHC3 and SHH signaling pathways in the lung cancer stem cells. In addition, SFN combined with Knock-down of Shh gene showed a greater effect on the proliferation of lung cancer cells. Conclusion: SFN is an effective new drug which can inhibit proliferation of lung cancer stem cells through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung cancer stem cells.

scholarly journals Signaling Pathways Associated with Cancer Stem Cells Play a Significant Role in Immunotherapy Resistance

2019 ◽  
Vol 1 (2) ◽  
Author(s):  
Yajuan Zhu ◽  
Yuwen Zhou ◽  
Yao Xie ◽  
Pan Song ◽  
Xuelei Ma
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Tumor Recurrence ◽  
Underlying Mechanism ◽  
Self Renewal ◽  
Persistent Problem ◽  
Immune Resistance

Cancer stem cells (CSCs) are a subpopulation of tumor cells with properties of self-renewal, pluripotency, plasticity, and differentiation, and are associated with various aberrantly stimulated signaling pathways. They are responsible for tumor recurrence, distant metastasis, and drug resistance, thus inducing poor prognosis. Immunotherapy has achieved encouraging results. However, the resistance associated with its clinical application is a persistent problem in clinical and scientific researches. Increasing evidence shows that signaling pathways associated with CSCs mediate immunotherapy resistance. This review highlights the link between them, and focuses on the underlying mechanism so as to provide potential strategies and approaches for the development of new targets against the immune resistance challenge.

scholarly journals Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 840 ◽  
Author(s):  
Abdul Khan ◽  
Eiman Ahmed ◽  
Noor Elareer ◽  
Kulsoom Junejo ◽  
Martin Steinhoff ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Clinical Outcome ◽  
Cancer Treatment ◽  
Signaling Pathways ◽  
Cancer Resistance ◽  
Oncogenic Signaling ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known to regulate expression of more than 60% of the human genes, and their aberrant expression has been associated with the pathogenesis of human cancers and the regulation of stemness features of CSCs. CSCs are the small population of cells present in human malignancies well-known for cancer resistance, relapse, tumorigenesis, and poor clinical outcome which compels the development of novel and effective therapeutic protocols for better clinical outcome. Interestingly, the role of miRNAs in maintaining and regulating the functioning of CSCs through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/β-Catenin, janus kinases/ signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-kB), is critical and poses a huge challenge to cancer treatment. Based on recent findings, here, we have documented the regulatory action or the underlying mechanisms of how miRNAs affect the signaling pathways attributed to stemness features of CSCs, such as self-renewal, differentiation, epithelial to mesenchymal transition (EMT), metastasis, resistance and recurrence etc., associated with the pathogenesis of various types of human malignancies including colorectal cancer, lung cancer, breast cancer, head and neck cancer, prostate cancer, liver cancer, etc. We also shed light on the fact that the targeted attenuation of deregulated functioning of miRNA related to stemness in human carcinogenesis could be a viable approach for cancer treatment.

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