scholarly journals Antioxidant Mechanisms and ROS-Related MicroRNAs in Cancer Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Ilaria Dando ◽  
Marco Cordani ◽  
Elisa Dalla Pozza ◽  
Giulia Biondani ◽  
Massimo Donadelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Biological Process ◽  
Oxygen Species ◽  
Poor Clinical Outcome ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Induced Stress ◽  
Antioxidant Mechanisms

Increasing evidence indicates that most of the tumors are sustained by a distinct population of cancer stem cells (CSCs), which are responsible for growth, metastasis, invasion, and recurrence. CSCs are typically characterized by self-renewal, the key biological process allowing continuous tumor proliferation, as well as by differentiation potential, which leads to the formation of the bulk of the tumor mass. CSCs have several advantages over the differentiated cancer cell populations, including the resistance to radio- and chemotherapy, and their gene-expression programs have been shown to correlate with poor clinical outcome, further supporting the relevance of stemness properties in cancer. The observation that CSCs possess enhanced mechanisms of protection from reactive oxygen species (ROS) induced stress and a different metabolism from the differentiated part of the tumor has paved the way to develop drugs targeting CSC specific signaling. In this review, we describe the role of ROS and of ROS-related microRNAs in the establishment and maintenance of self-renewal and differentiation capacities of CSCs.

scholarly journals MicroRNA-28-5p Regulates Liver Cancer Stem Cell Expansion via IGF-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Qing Xia ◽  
Tao Han ◽  
Pinghua Yang ◽  
Ruoyu Wang ◽  
Hengyu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Critical Role ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
The Impact

Background. MicroRNAs (miRNAs) play a critical role in the regulation of cancer stem cells (CSCs). However, the role of miRNAs in liver CSCs has not been fully elucidated. Methods. Real-time PCR was used to detect the expression of miR-miR-28-5p in liver cancer stem cells (CSCs). The impact of miR-28-5p on liver CSC expansion was investigated both in vivo and in vitro. The correlation between miR-28-5p expression and sorafenib benefits in HCC was further evaluated in patient-derived xenografts (PDXs). Results. Our data showed that miR-28-5p was downregulated in sorted EpCAM- and CD24-positive liver CSCs. Biofunctional investigations revealed that knockdown miR-28-5p promoted liver CSC self-renewal and tumorigenesis. Consistently, miR-28-5p overexpression inhibited liver CSC’s self-renewal and tumorigenesis. Mechanistically, we found that insulin-like growth factor-1 (IGF-1) was a direct target of miR-28-5p in liver CSCs, and the effects of miR-28-5p on liver CSC’s self-renewal and tumorigenesis were dependent on IGF-1. The correlation between miR-28-5p and IGF-1 was confirmed in human HCC tissues. Furthermore, the miR-28-5p knockdown HCC cells were more sensitive to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrated that the miR-28-5p may predict sorafenib benefits in HCC patients. Conclusion. Our findings revealed the crucial role of the miR-28-5p in liver CSC expansion and sorafenib response, rendering miR-28-5p an optimal therapeutic target for HCC.

The Role of Nrf2 signaling in cancer stem cells: From stemness and self-renewal to tumorigenesis and chemoresistance

Life Sciences ◽  
2019 ◽  
Vol 239 ◽  
pp. 116986 ◽  
Author(s):  
Houman Kahroba ◽  
Masoud Shirmohamadi ◽  
Mohammad Saeid Hejazi ◽  
Nasser Samadi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Self Renewal

scholarly journals Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells

2016 ◽  
Vol 48 (8) ◽  
pp. e255-e255 ◽  
Author(s):  
Dae Kyoung Kim ◽  
Eun Jin Seo ◽  
Eun J Choi ◽  
Su In Lee ◽  
Yang Woo Kwon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Crucial Role ◽  
The Self ◽  
Ovarian Cancer Stem Cells ◽  
Self Renewal

scholarly journals ID3010 Wnt antagonism in cancer stem cells- targeting stemness of cancers via the Wnt-BETA catenin pathway

2017 ◽  
Vol 4 (S) ◽  
pp. 23
Author(s):  
Sudha Warrier
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Somatic Tissue ◽  
Beta Catenin ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Epithelial Cancers ◽  
Multiple Levels

Cancer stem cells (CSCs) are hypothesized to be the pathological counterpart of normal somatic tissue stem cells. The CSC model proposes that tumours are hierarchically  organised with a subset of tumour cells at their apex, which possess self-renewal and multilineage differentiation potential. Cancer stem cells, unlike the bulk of the cells within the tumor, are elusive to drug treatment and are unaffected on chemo and radiotherapy. These self-renewing cells are responsible for the flare up of cancer and remission long after treatment. Cancer stem cells have a capacity for unlimited self-renewal, as well as the ability to initiate and drive tumor progression in an animal model.  Activated Wnt/β-Catenin signaling is a key feature of epithelial cancers and is critical for metastasis and epithelial-mesenchymal transition (EMT) , a signature trait of CSCs. We explored the effect of the Wnt antagonist, secreted frizzled related protein 4 (sFRP4) in CSCs in gliomas. We found that sFRP4 chemo-sensitizes GSC-enriched cells to commonly used drugs, by the reversal of EMT and by decreasing drug effluxers. sFRP4 acts at multiple levels of the Wnt- β-Catenin and the Wnt- calcium pathways in inhibiting CSCs. We also identified a novel mechanism of action of sFRP4. These findings could be exploited for designing better targeted strategies to improve chemo-response and eventually eliminate glioblastoma CSCs.

scholarly journals PS1 - 158 The Role of LIN28A in Neoplastic Transformation of Human Embryonic Stem Cells (hESCs)

2016 ◽  
Vol 43 (S4) ◽  
pp. S10-S10
Author(s):  
R. Kaur ◽  
L. Liang ◽  
T. Werbowetski-Ogilvie
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Rna Binding ◽  
Embryonic Stem ◽  
Neoplastic Transformation ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Human Cancers

Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.

scholarly journals A2 KRT15+ TUMOR CELLS AS PUTATIVE CANCER STEM CELLS IN ESOPHAGEAL CANCER.

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 2-3
Author(s):  
J Douchin ◽  
V Giroux
Keyword(s):  
Stem Cells ◽  
Esophageal Cancer ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Treatment Resistance ◽  
Esophageal Tumor ◽  
Basal Cells ◽  
Cell Of Origin ◽  
Self Renewal

Abstract Background Esophageal cancer is a particularly deadly cancer with a 5-year survival rate of only 14% in Canada. Treatment resistance ascribed for at least 30% of the death. The acquisition of resistance to radio- and chemotherapy is mostly attributed to the presence of cancer stem cells (CSCs) and their persistence following classical treatments. CSCs are a subpopulation of tumor cells with high self-renewal and multipotent capacity which amongst others contribute to tumor heterogeneity. Our previous work identified Krt15+ esophageal cells as a rare and long-lived subpopulation of basal cells with higher self-renewal and multipotent capacities than other basal cells. Furthermore, preliminary observations suggest that Krt15+ cells could act as the cell-of-origin for ESCC, the most prevalent type of esophageal cancer worldwide. Though, we still ignore the role of Krt15+ cells in later stages of esophageal cancer such as treatment resistance and if therefore, they could act as CSC. Aims Determine if Krt15+ cells act as CSCs in ESCC patients and if they could contribute to treatment resistance. Methods To do so, we used Krt15-CrePR1;R26mT/mG mice treated with the carcinogen 4 Nitroquinoline-1-oxide (4NQO) in their drinking water for 16 weeks to induce ESCC. Twelve weeks following the beginning of 4NQO treatment, we induced Cre recombination with RU486, a PR1 agonist, leading to GFP expression specifically in Krt15+ cells. Following 4NQO treatment, mice were put back on normal water for 8 to 12 weeks allowing tumors to grow. At euthanasia, esophageal tumor cells were FACS sorted to isolate Krt15+ (GFP+) and Krt15- (GFP-) cells, which were then grown as tumoroids. Results We first validated that 4NQO successfully induced the formation of esophageal lesions in our model, which comprises Krt15+ and Krt15- tumor cells. Tumoroids were then successfully derived from these FACS-sorted cell populations. We demonstrated the increase of CSC-like cells within Krt15+ tumoroids compared to Krt15- tumoroids by measuring the presence of CD44highCD24high cells, two well-known CSC markers, by flow cytometry. Interestingly, Krt15+ and Krt15- tumoroids are histologically distinct. As observed for normal cells, Krt15+ tumoroids appeared as more multipotent and heterogenous than Krt15- tumoroids. Furthermore, Krt15+ tumoroids display higher hyperplasia than Krt15- tumoroids suggesting that Krt15+ tumor cells are functionally distinct from Krt15- tumor cells. Conclusions Krt15+ tumoroids display higher CSC content and hyperplastic capacity suggesting their potential role in esophageal cancer. With this project, we aim to highlight the role of Krt15+ cells in treatment resistance and put forward new targets to overcome this deadly issue in ESCC patients. Funding Agencies CAGCanada research chair TIER 2

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