scholarly journals MYC Regulates the HIF2α Stemness Pathway via Nanog and Sox2 to Maintain Self-Renewal in Cancer Stem Cells versus Non-Stem Cancer Cells

2019 ◽  
Vol 79 (16) ◽  
pp. 4015-4025 ◽  
Author(s):  
Bikul Das ◽  
Bidisha Pal ◽  
Rashmi Bhuyan ◽  
Hong Li ◽  
Anupam Sarma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Self Renewal

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 Immunotherapy: Newer Therapeutic Armamentarium against Cancer Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Saurabh Pratap Singh ◽  
Richa Singh ◽  
Om Prakash Gupta ◽  
Shalini Gupta ◽  
Madan Lal Brahma Bhatt
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Effective Means ◽  
Treatment Strategies ◽  
Antigen Expression ◽  
Therapy Resistance ◽  
Treatment Modalities ◽  
Self Renewal ◽  
Primary Tumors

Mounting evidence from the literature suggests the existence of a subpopulation of cancer stem cells (CSCs) in almost all types of human cancers. These CSCs possessing a self-renewal capacity inhabit primary tumors and are more defiant to standard antimitotic and molecularly targeted therapies which are used for eliminating actively proliferating and differentiated cancer cells. Clinical relevance of CSCs emerges from the fact that they are the root cause of therapy resistance, relapse, and metastasis. Earlier, surgery, chemotherapy, and radiotherapy were established as cancer treatment modalities, but recently, immunotherapy is also gaining importance in the management of various cancer patients, mostly those of the advanced stage. This review abridges potential off-target effects of inhibiting CSC self-renewal pathways on immune cells and some recent immunological studies specifically targeting CSCs on the basis of their antigen expression profile, even though molecular markers or antigens that have been described till date as expressed by cancer stem cells are not specifically expressed by these cells which is a major limitation to target CSCs. We propose that owing to CSC stemness property to mediate immunotherapy response, we can apply a combination therapy approach by targeting CSCs and tumor microenvironment (TME) along with conventional treatment strategies as an effective means to eradicate cancer cells.

scholarly journals Sulforaphane inhibits self-renewal of lung cancer stem cells through the modulation of sonic Hedgehog signaling pathway and polyhomeotic homolog 3

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fanping Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Lung Cancer Cells ◽  
Sonic Hedgehog Signaling ◽  
Self Renewal ◽  
Lung Cancer Stem Cells

AbstractSulforaphane (SFN), an active compound in cruciferous vegetables, has been characterized by its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. CD133+ cells were isolated with MACs from lung cancer A549 and H460 cells. In this study, we found that SFN inhibited the proliferation of lung cancer cells and self-renewal of lung cancer stem cells simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in CD133+ lung cancer cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of CD133+ lung cancer cells, and decreased the protein expression of PHC3 in CD133+ lung cancer cells. Knock-down of PHC3 also affected the proliferation and decreased the Shh expression level in CD133+ lung cancer cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in CD133+ lung cancer cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-Shh and siRNA-PHC3 cells was weaker than that on the proliferation of siRNA-control cells. Sonic Hedgehog signaling pathway might undergo a cross-talk with PHC3 in self-renewal of lung cancer stem cells. SFN might be an effective new drug which could inhibit self-renewal of lung cancer stem cells through the modulation of Sonic Hedgehog signaling pathways and PHC3. This study could provide a novel way to improve therapeutic efficacy for lung cancer stem cells.

scholarly journals The Impact of Iron Chelators on the Biology of Cancer Stem Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 89
Author(s):  
Julia Szymonik ◽  
Kamila Wala ◽  
Tomasz Górnicki ◽  
Jolanta Saczko ◽  
Bartosz Pencakowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Iron Chelators ◽  
Neoplastic Disease ◽  
Self Renewal ◽  
Novel Drugs ◽  
Cell Progression ◽  
The Impact ◽  
Transcription Factor Proteins

Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells’ maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.

Pancreatic Cancer Stem Cells

2008 ◽  
Vol 26 (17) ◽  
pp. 2806-2812 ◽  
Author(s):  
Cheong J. Lee ◽  
Joseph Dosch ◽  
Diane M. Simeone
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Specific Antigen ◽  
Solid Organ ◽  
Self Renewal ◽  
Pancreatic Cancer Cells ◽  
Specific Subset ◽  
Pancreatic Cancer Stem Cells

Cellular heterogeneity in cancer was observed decades ago by studies in mice which showed that distinct subpopulations of cells within a tumor mass are capable of driving tumorigenesis. Conceptualized from this finding was the stem-cell hypothesis for cancer, which suggests that only a specific subset of cancer cells within each tumor is responsible for tumor initiation and propagation, termed tumor initiating cells or cancer stem cells (CSCs). Recent data has been provided to support the existence of CSCs in human blood cell–derived cancers and solid organ tumors of the breast, brain, prostate, colon, and skin. Study of human pancreatic cancers has also revealed a specific subpopulation of cancer cells that possess the characteristics of CSCs. These pancreatic cancer stem cells express the cell surface markers CD44, CD24, and epithelial-specific antigen, and represent 0.5% to 1.0% of all pancreatic cancer cells. Along with the properties of self-renewal and multilineage differentiation, pancreatic CSCs display upregulation of important developmental genes that maintain self-renewal in normal stem cells, including Sonic hedgehog (SHH) and BMI-1. Signaling cascades that are integral in tumor metastasis are also upregulated in the pancreatic CSC. Understanding the biologic behavior and the molecular pathways that regulate growth, survival, and metastasis of pancreatic CSCs will help to identify novel therapeutic approaches to treat this dismal disease.

scholarly journals Redox Regulation in Cancer Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Shijie Ding ◽  
Chunbao Li ◽  
Ninghui Cheng ◽  
Xiaojiang Cui ◽  
Xinglian Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Redox Regulation ◽  
Cancer Recurrence ◽  
Ros Generation ◽  
Self Renewal ◽  
Cellular Processes

Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs). We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment.

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Sonic Hedgehog Signaling Pathway and Polyhomeotic Homolog3

2021 ◽  
Author(s):  
FanPing Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract 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 (CSCs). CD133-positive lung cancer cells were isolated by MACs from lung cancer A549 and H460 cells. And then, the expression of CD133 was measured by flow cytometry assays (FACS). The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The mRNA expression of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) was measured by quantitative reverse transcription polymerase chain reaction (QPCR). And the protein expression of Shh, Smo, Gli1 and PHC3 was determined by western blotting. Shh was knocked down by siRNA to further study the role of Shh signaling pathways in lung CSCs. SFN inhibited the proliferation of lung cancer cells and lung CSCs simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in A549 /CD133+ and H460 /CD133+ cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of A549/ CD133+ and H460/ CD133+ cells, and decreased the protein expression of PHC3 in A549/ CD133+ and H460/ CD133+ cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in A549/ CD133+ and H460/ CD133+ cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-shh cells is weaker than that of siRNA-control cells. SFN is an effective new drug which can inhibit proliferation of lung CSCs through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung CSCs.

scholarly journals Betavulgarin Isolated from Sugar Beet (Beta vulgaris) Suppresses Breast Cancer Stem Cells through Stat3 Signaling

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 2999
Author(s):  
Ren Liu ◽  
Hack Sun Choi ◽  
Xing Zhen ◽  
Su-Lim Kim ◽  
Ji-Hyang Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Gel Filtration ◽  
Resonance Spectroscopy ◽  
Breast Cancer Stem Cells ◽  
Self Renewal ◽  
Major Health Problem

Breast cancer is a major health problem that affects lives worldwide. Breast cancer stem cells (BCSCs) are small subpopulations of cells with capacities for drug resistance, self-renewal, recurrence, metastasis, and differentiation. Herein, powder extracts of beetroot were subjected to silica gel, gel filtration, thin layer chromatography (TLC), and preparatory high-pressure liquid chromatography (HPLC) for isolation of one compound, based on activity-guided purification using tumorsphere formation assays. The purified compound was identified as betavulgarin, using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI) mass spectrometry. Betavulgarin suppressed the proliferation, migration, colony formation, and mammosphere formation of breast cancer cells and reduced the size of the CD44+/CD24− subpopulation and the expression of the self-renewal-related genes, C-Myc, Nanog, and Oct4. This compound decreased the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3) and reduced the mRNA and protein levels of sex determining region Y (SRY)-box 2 (SOX2), in mammospheres. These data suggest that betavulgarin inhibit the Stat3/Sox2 signaling pathway and induces BCSC death, indicating betavulgarin might be an anticancer agent against breast cancer cells and BCSCs.

scholarly journals SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1

2020 ◽  
Author(s):  
Cong Tian ◽  
Tingyuan Lang ◽  
Jiangfeng Qiu ◽  
Kun Han ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Drug Target ◽  
Self Renewal ◽  
Protein Levels ◽  
Colorectal Cancer Cells ◽  
Underlying Mechanisms ◽  
And Migration

Abstract Background: Cancer stem cells (CSCs) have been recognized as an important drug target, however, the underlying mechanisms have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 promotes colorectal cancer (CRC) stem cells (CRC-SCs) and the underlying mechanisms have remained elusive.Methods: Human CRC cell lines HCT-116 and HT-29 and primary human colorectal cancer cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels were examined by qRT-PCR and western blot, respectively. Sphere formation and transwell assay were employed for examination of sphere-forming and migration capacities. The self-renewal capacity was determined by limiting dilution assay. The tumorigenicity was examined by xenograft model. The transcriptional activities of the promoters were examined by luciferase reporter assay. Co-immunoprecipitation assay was used to test protein-protein interaction. The transcription and protein-DNA interaction were examined by nuclear run-on and ChIP-PCR assay. The relationship between gene expression and survival was analyzed by Kaplan-meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± s.d. and the significance was determined by Student’s t-test.Results: SKP1 is upregulated in colorectal cancer stem cells and predicts poor prognosis of colon cancer patients. Overexpression of SKP1 promotes the sphere-forming and migration capacities as well as self-renewal of CRC cells, and upregulates the expression of CSCs markers. In contrast, SKP1 depletion produces the opposite effects. SKP1 strengthens YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of colorectal cancer cells. SKP1 suppresses RASSF1 at both mRNA and protein levels and overexpression of RASSF1 abolished the effect of SKP1.Conclusion: Our results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of CRC cells. Our works thus revealed a novel underlying mechanism of CRC-SCs maintenance and suggested a novel drug target for eradicating CRC-SCs.

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