p53 and Cell Fate: Sensitizing Head and Neck Cancer Stem Cells to Chemotherapy

Rodriguez-Ramirez, Christie

doi:10.1615/critrevoncog.2018027353

Cited by 12 publications

(11 citation statements)

References 150 publications

(154 reference statements)

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“…166 Furthermore, recent studies have shown that the expansion, depletion or maintenance of the stem cell pool are regulated through symmetric and asymmetric division events. [167][168][169] Failure to properly control cell division patterns can lead to premature depletion of the stem cell pool or to abnormal growth and differentiation disorders that accelerate cellular senescence. 168 Cell polarity proteins are potential key regulators of asymmetric cell division, and a reduction in or loss of asymmetric cell division may be associated with diseases common to the aging process.…”

Section: Epigenetic Alterationsmentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

363

160

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Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. Although the development of modern medicine has promoted human health and greatly extended life expectancy, with the aging of society, a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals. Current research on aging focuses on elucidating how various endogenous and exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss of proteostasis, compromise of autophagy, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing) participate in the regulation of aging. Furthermore, thorough research on the pathogenesis of aging to identify interventions that promote health and longevity (such as caloric restriction, microbiota transplantation, and nutritional intervention) and clinical treatment methods for aging-related diseases (depletion of senescent cells, stem cell therapy, antioxidative and anti-inflammatory treatments, and hormone replacement therapy) could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.

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Section: Epigenetic Alterationsmentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

363

160

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“…So, EGLN1 could downregulate the expression of p53 through the ubiquitination system in a manner different from that exhibited by other family members. It is worth noting that p53 is known to be a tumor suppressor which inhibits oncogenesis and self-renewal during tumorigenesis, posing an obstacle to the formation of CSCs [25]. Cancer stem cells are defined as a population of cancer cells with the ability of self-renewal and high capacity for tumorigenicity.…”

Section: Discussionmentioning

confidence: 99%

EGLN1 induces tumorigenesis and radioresistance in nasopharyngeal carcinoma by promoting ubiquitination of p53 in a hydroxylase-dependent manner

Sun¹,

Wu²,

Jun³

et al. 2022

J. Cancer

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Egl-9 Family Hypoxia Inducible Factor 1 (EGLN1) is a proline hydroxylase mediating degradation of hypoxia-inducible factor α (HIFα) through the ubiquitination system. Studies have indicated an essential role for EGLN1 in angiogenesis and tumorigenesis. However, there is no consensus on the regulation of EGLN1 and its mechanism of action on nasopharyngeal carcinoma (NPC). This study explored the association of the expression of EGLN1 with characteristics of NPC tumors and its underlying mechanism. We found that the expression of EGLN1 showed a positive correlation with tumor T classification and clinical staging of patients with NPC. EGLN1 could promote cell proliferation, invasion and migration, and even enhance the cancer stem cells (CSCs) prosperity and radioresistance of NPC cells. Mechanistically, EGLN1 facilitated degradation of tumor protein p53 through the ubiquitination system. This effect could be weakened in the presence of dimethyloxalylglycine (DMOG), suggesting that EGLN1 down-regulated p53 based on its hydroxylase activity. In conclusion, overexpression of EGLN1 promoted oncogenesis and induced a CSC-like phenotype in NPC cells, then enhancing the ability for radioresistance by interacting with p53 in a hydroxylase-dependent manner. Thus, EGLN1 might serve as a potential therapeutic target for NPC.

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“…Thus, transcription factors that had the likelihood to bind with the promoter regions of WT1-AS were predicted. Among these transcription factors, TP53 [26,30] and XBP1 [27,28,31] were found to be implicated in the formation and development of cancer stem cells. Our experiments demonstrated that TP53 increase did not in uence WT1-AS expression in GSCs.…”

Section: Discussionmentioning

confidence: 99%

Investigations into the effects and related upstream/downstream regulatory mechanisms of long non-coding RNA WT1-AS in the maintenance and development of gastric cancer stem cells in vitro and in vivo

Zhang¹,

Jin²,

Liu³

et al. 2021

Preprint

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Background Cancer stem cells (CSCs) are proposed to be responsible for almost all malignant phenotypes (e.g. heterogeneity, uncontrolled growth, metastasis, recurrence, chemoresistance) of tumors. Long non-coding RNA WT1 antisense RNA (WT1-AS) has been found to be involved in the regulation of lung cancer cell stemness. However, the roles and molecular mechanisms of WT1-AS in the maintenance and development of gastric cancer stem cells (GSCs) have not been investigated. Methods mRNA and protein expression was measured by RT-qPCR and western blot. CCK8 and Soft agar colony formation assays were performed to assess cell viability and colony clone formation ability. Cell cycle and apoptosis were determined by flow cytometry analysis. Cell transwell and wound healing analyses were carried out to assess cell migration ability. In vitro angiogenesis and 3D spheroid cultures assays were also performed. Moreover, in vitro experiments were carried out to explore the function of WT1-AS on tumor growth, metastasis and cell stemness. The upstream transcription factors or downstream genes of WT1-AS were screened through Bioinformatics, dual-luciferase assays and RNA-sequencing (RNA-seq) technology. Results Our present study demonstrated that WT1-AS knockdown or wilms tumor 1 (WT1) overexpression improved GSC proliferative and migratory capacities, promoted GSC EMT, enhanced GSC stemness, inhibited GSC apoptosis, potentiated the resistance of GSCs to 5-FU and induced HUVEC angiogenesis in vitro. WT1-AS loss or WT1 increase facilitated the formation of in-vitro 3D GSC aggregates. WT1-AS ameliorated the malignant phenotypes of GSCs by down-regulating WT in vitro. Additionally, WT1-AS inhibited tumor growth and metastasis, and reduced tumor stemness in GSCs-derived xenografts (s.c., i.p., and i.v.) in vivo. Furthermore, XBP1 was identified as an upstream regulator of WT1-AS in GSCs. RNA-seq and RT-qPCR data suggested that PSPH, GSTO2, FYN, and PHGDH might be the downstream targets of WT1-AS in GSCs. Conclusions Our data demonstrated that WT1-AS weakened the stem-cell like behaviors and characteristics of GSCs in vitro and in vivo by down-regulating WT1. Also, some upstream regulators and downstream targets of WT1-AS were identified in GSCs. Investigations on the molecular mechanisms underlying the complex phenotypes of GSCs might contribute to the better management of headaches in cancers.

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p53 and Cell Fate: Sensitizing Head and Neck Cancer Stem Cells to Chemotherapy

Cited by 12 publications

References 150 publications

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

EGLN1 induces tumorigenesis and radioresistance in nasopharyngeal carcinoma by promoting ubiquitination of p53 in a hydroxylase-dependent manner

Investigations into the effects and related upstream/downstream regulatory mechanisms of long non-coding RNA WT1-AS in the maintenance and development of gastric cancer stem cells in vitro and in vivo

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