NF-κB Participates in the Stem Cell Phenotype of Ovarian Cancer Cells

González-Torres, Carolina; Gaytán-Cervantes, Javier; Vázquez-Santillán, Karla; Mandujano-Tinoco, Edna Ayerim; Ceballos‐Cancino, Gisela; García-Venzor, Alfredo; Zampedri, Cecilia; Sanchez-Maldonado, Paulina; Mojica-Espinosa, Raúl; Jimenez-Hernandez, Luis Enrique; Maldonado, Vilma

doi:10.1016/j.arcmed.2017.08.001

Cited by 47 publications

(40 citation statements)

References 33 publications

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“…CD44 + cells promote self-renewal, metastasis, and maintenance of ovarian CSCs by increasing the expression of RelA, RelB, and IKKα and mediating nuclear activation of p50/RelA (p50/ p65) dimer. 290 High levels of NIK induce activation of the noncanonical NF-κB pathway to regulate the self-renewal and metastasis of breast CSCs. 291 Moreover, stromal cell-derived factor-1 (SDF-1) also has the same effect by regulating the translocation of p65 from the cytoplasm to the nucleus.…”

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

1,323

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%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,323

998

View full text Add to dashboard Cite

show abstract

“…Signal transduction pathways have been shown to maintain the CSC phenotype in OC [79]. Several pathways, including those involving PI3/PTEN/AKT [80], JAK2/STAT3 [81][82][83], NFkB [84,85], Notch [86,87], Wnt [86,87], and Hedgehog [86,88] support the CSC phenotype and promote tumourigensis and therapy resistance in OC. Inhibiting these pathways in ovarian cell lines and OC animal models suppresses CSC numbers and makes these cells sensitive to chemotherapies [79].…”

Section: Epigenetic Changesmentioning

confidence: 99%

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ahmed

Kadife²,

Raza

et al. 2020

Cells

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Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease. of 35have been observed in OC patients but not in patients with benign and borderline tumours, and this hypomethylation correlates with advanced-stage disease and poor prognosis [48,49]. A genome-wide methylation profiling of blood cells from healthy controls and age-matched untreated OC patients identified CpG methylation of 2714 cancer-related genes, of which 56% were hypomethylated [50]. Ovarian Cancer Stem CellsCellular heterogeneity associated with genetic and epigenetic changes in tumours are linked with the initiation and expansion of CSCs, a population of cells within the tumour, which initiate tumour growth through self-renewal and differentiation processes [51,52]. These cells are more adaptive to the changing tumour microenvironment and tend to be more resistant to treatment. CSCs are highly plastic and a few numbers of isolated CSCs have been shown to be responsible for tumorgenesis and are more chemotherapy and radiation resistant due to their dormant state and a high expression of drug efflux pumps [53,54]. As a result, CSCs are able to adapt to different tumour microenvironments and survive due to their efficient DNA repair mechanisms and their capacity to evade host immune surveillance [55][56][57]. These inherent properties of CSCs suggest an active role in tumour relapse and emphasize the need to develop effective targeted therapies to improve clinical outcomes in patients [51][52][53][54][55][56][57].Stem cells have been identified in ovaries and fallopian tubes [58,59]. These cells express proteins including aldehyde dehydrogenase family 1 A2 (ALDH1A2), homeobox protein NANOG, LIM homeobox protein 9 (LHX9) and frizzled-related protein 1 (SRFP1) and have been observed in OSE, CIC and fimbria [2,[58][59][60][61][62]. In a...

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“…Many signaling pathways, including b-catenin, p38 MAPK, AKT, YAP, NF-jB, and STAT3, can affect the function of CSCs [21][22][23][24][25][26]. To elucidate how PGD2/PTGDR2 signaling inhibited GC stemness, we analyzed the phosphorylation and expression of key proteins in these pathways that may affect the role of CSCs.…”

Section: Pgd2/ptgdr2 Signaling Suppressed the Activation Of Stat3mentioning

confidence: 99%

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

Zhang

Bie

et al. 2018

Stem Cells

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The antitumor effect of prostaglandin D2 (PGD2) on gastric cancer (GC) has been known for decades. However, the mechanism of PGD2's control of GC growth is unclear. Cancer stem cells (CSCs) are implicated in tumor neovascularization, invasiveness, and therapeutic resistance. Herein, we discovered that signaling between PGD2 and its receptor (PTGDR2) has the ability to restrict the self-renewal of GC cells in vitro and suppress tumor growth and metastasis in vivo. To obtain these findings, we first determined that PGD2 synthase (L-PTGDS) and PTGDR2 expression were lower in GC tissues than adjacent tissues and was associated with the patients' prognosis. Moreover, the expression of L-PTGDS and PTGDR2 was negatively correlated with the GC-CSC markers Sall4 and Lgr5 in GC tissues. Second, L-PTGDS and PTGDR2 expression were knocked down in CSC-like cells, resulting in enhanced expression of CSC markers and self-renewal ability. Direct PGD2 stimulation and L-PTGDS overexpression produced the opposite effect. Thirdly, PGD2 inhibited tumor growth and incidence rate in a subcutaneous tumor model and suppressed liver and mesenteric metastasis in a peritoneal metastasis model. Interfering with the expression of PTGDR2 reversed these effects in vivo. Last, a mechanistic study found that PGD2 inhibited STAT3 phosphorylation and nuclear expression. Further experiments revealed that the inhibitory effect of PGD2 on the expression of CSC markers disappeared after mutations were introduced into STAT3 phosphorylation (Thr705) site. In short, this study reveals a novel function of PGD2/PTGDR2 signaling on CSC regulation and provides a new way to control the development of GC. Stem Cells 2018;36:990-1003.

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NF-κB Participates in the Stem Cell Phenotype of Ovarian Cancer Cells

Cited by 47 publications

References 33 publications

Targeting cancer stem cell pathways for cancer therapy

Targeting cancer stem cell pathways for cancer therapy

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer

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