scholarly journals Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories

MedChemComm ◽  
2017 ◽  
Vol 8 (1) ◽  
pp. 21-52 ◽  
Author(s):  
Anthony R. Martin ◽  
Cyril Ronco ◽  
Luc Demange ◽  
Rachid Benhida
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Cancer Stem Cells ◽  
Hypoxia Inducible Factor ◽  
Large Set ◽  
Down Regulation ◽  
Self Renewal ◽  
Hypoxia Inducible Factor 1 ◽  
Success Stories ◽  
Tumour Vascularization

In cancers, hypoxia inducible factor 1 (HIF-1) is an over-expressed transcription factor, which regulates a large set of genes involved in tumour vascularization, metastases, and cancer stem cells (CSCs) formation and self-renewal.

scholarly journals Role of hypoxia inducible factor-1 in cancer stem cells (Review)

2020 ◽  
Vol 23 (1) ◽  
pp. 1-1
Author(s):  
Qi Zhang ◽  
Zhenzhen Han ◽  
Yanbo Zhu ◽  
Jingcheng Chen ◽  
Wei Li
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1

scholarly journals Hypoxia, Inflammation and Necrosis as Determinants of Glioblastoma Cancer Stem Cells Progression

2020 ◽  
Vol 21 (8) ◽  
pp. 2660
Author(s):  
Marco Papale ◽  
Mariachiara Buccarelli ◽  
Cristiana Mollinari ◽  
Matteo A. Russo ◽  
Roberto Pallini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Hypoxia Inducible Factor ◽  
Human Tumor ◽  
Metastatic Potential ◽  
Cellular Adhesion ◽  
Brain Invasion ◽  
Hypoxia Inducible Factor 1 ◽  
Tumor Tissues

Tumor hypoxic microenvironment causes hypoxia inducible factor 1 alpha (HIF-1α) activation and necrosis with alarmins release. Importantly, HIF-1α also controls the expression of alarmin receptors in tumor cells that can bind to and be activated by alarmins. Human tumor tissues possess 1–2% of cancer stem cells (CSCs) residing in hypoxic niches and responsible for the metastatic potential of tumors. Our hypothesis is that hypoxic CSCs express alarmin receptors that can bind alarmins released during necrosis, an event favoring CSCs migration. To investigate this aspect, glioblastoma stem-like cell (GSC) lines were kept under hypoxia to determine the expression of hypoxic markers as well as receptor for advanced glycation end products (RAGE). The presence of necrotic extracts increased migration, invasion and cellular adhesion. Importantly, HIF-1α inhibition by digoxin or acriflavine prevented the response of GSCs to hypoxia alone or plus necrotic extracts. In vivo, GSCs injected in one brain hemisphere of NOD/SCID mice were induced to migrate to the other one in which a necrotic extract was previously injected. In conclusion, our results show that hypoxia is important not only for GSCs maintenance but also for guiding their response to external necrosis. Inhibition of hypoxic pathway may therefore represent a target for preventing brain invasion by glioblastoma stem cells (GSCs).

scholarly journals Unraveling the origin of Glucose mediated disparate proliferation dynamics of Cancer stem cells

2021 ◽  
Author(s):  
Tagari Samanta ◽  
Sandip Kar
Keyword(s):  
Mathematical Model ◽  
Stem Cells ◽  
Transcription Factor ◽  
Cancer Stem Cells ◽  
Therapeutic Strategies ◽  
Dependent Manner ◽  
Self Renewal ◽  
Expression Levels ◽  
Context Dependent ◽  
Fine Tune

AbstractCancer stem cells (CSCs) often switch on their self-renewal programming aggressively to cause a relapse of cancer. Intriguingly, glucose differentially triggers the proliferation propensities in CSCs in an origin-dependent manner by controlling the expression of the key transcription factor like Nanog. However, the factors that critically govern this glucose-stimulated proliferation dynamics of CSCs remains elusive. Herein, by proposing a mathematical model of glucose-mediated Nanog regulation in CSCs, we showed that the differential proliferation behavior of CSCs can be explained by considering the experimentally observed varied expression levels of key positive (STAT3) and negative (p53) regulators of Nanog. Our model reconciles various experimental observations and predicts ways to fine-tune the proliferation dynamics of specific CSCs in a context-dependent manner. In future, these modeling insights will be useful in developing improved therapeutic strategies to get rid of harmful CSCs.

Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway

2020 ◽  
Vol 23 (26) ◽  
pp. 2945-2959 ◽  
Author(s):  
Xiangping Deng ◽  
Yijiao Peng ◽  
Jingduo Zhao ◽  
Xiaoyong Lei ◽  
Xing Zheng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Pharmacological Activities ◽  
Hypoxia Inducible Factor 1 ◽  
The Past ◽  
Low Toxicity ◽  
Tumor Blood Vessels

Rapid tumor growth is dependent on the capability of tumor blood vessels and glycolysis to provide oxygen and nutrients. Tumor hypoxia is a common characteristic of many solid tumors, and it essentially happens when the growth of the tumor exceeds the concomitant angiogenesis. Hypoxia-inducible factor 1 (HIF-1) as the critical transcription factor in hypoxia regulation is activated to adapt to this hypoxia situation. Flavonoids, widely distributed in plants, comprise many polyphenolic secondary metabolites, possessing broadspectrum pharmacological activities, including their potentiality as anticancer agents. Due to their low toxicity, intense efforts have been made for investigating natural flavonoids and their derivatives that can be used as HIF-1α inhibitors for cancer therapy during the past few decades. In this review, we sum up the findings concerning the inhibition of HIF-1α by natural flavonoids in the last few years and propose the idea of designing tumor vascular and glycolytic multi-target inhibitors with HIF-1α as one of the targets.

Integrin α6 (CD49f), The Microenvironment and Cancer Stem Cells

2019 ◽  
Vol 14 (5) ◽  
pp. 428-436 ◽  
Author(s):  
Gabriele D. Bigoni-Ordóñez ◽  
Daniel Czarnowski ◽  
Tyler Parsons ◽  
Gerard J. Madlambayan ◽  
Luis G. Villa-Diaz
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
The Self ◽  
Self Renewal ◽  
Terminal Disease

Cancer is a highly prevalent and potentially terminal disease that affects millions of individuals worldwide. Here, we review the literature exploring the intricacies of stem cells bearing tumorigenic characteristics and collect evidence demonstrating the importance of integrin α6 (ITGA6, also known as CD49f) in cancer stem cell (CSC) activity. ITGA6 is commonly used to identify CSC populations in various tissues and plays an important role sustaining the self-renewal of CSCs by interconnecting them with the tumorigenic microenvironment.

Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

2020 ◽  
Vol 15 ◽  
Author(s):  
Nese Unver
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Inflammatory Factors ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Inflammatory Stress ◽  
Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

scholarly journals Targeting the Roots of Recurrence: New Strategies for Eliminating Therapy-Resistant Breast Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 54
Author(s):  
Margaret L. Dahn ◽  
Paola Marcato
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells ◽  
Self Renewal ◽  
New Strategies

Cancer stem cells (CSCs) are functionally defined in our laboratories by their impressive tumor-generating and self-renewal capacity; clinically, CSCs are of interest because of their enhanced capacity to evade conventional therapies [...]

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