Circadian clock, carcinogenesis, chronochemotherapy connections

Yang, Yanyan; Lindsey-Boltz, Laura A.; Vaughn, Courtney M.; Selby, Christopher P.; Cao, Xuemei; Liu, Zhenxing; Hsu, David S.; Sancar, Aziz

doi:10.1016/j.jbc.2021.101068

Cited by 45 publications

(38 citation statements)

References 106 publications

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“…Different studies have established a relation between alterations in circadian rhythm genes and cancer [32,34]. Specifically, one of the genes associated with different types of cancer is cry [35][36][37]. Thus, this study aims to investigate the role of cry in a Drosophila GB model.…”

Section: Discussionmentioning

confidence: 99%

Circadian Gene cry Controls Tumorigenesis through Modulation of Myc Accumulation in Glioblastoma Cells

Jarabo¹,

Pablo²,

González-Blanco³

et al. 2022

IJMS

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Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. This aggressive tumor grows fast and spreads through the brain causing death in 15 months. GB cells display a high mutation rate and generate a heterogeneous population of tumoral cells that are genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We used a Drosophila model of GB that reproduces the features of human GB and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We studied the contribution of cry to the expansion of GB cells and the neurodegeneration and premature death caused by GB, and we determined that cry is required for GB progression. Moreover, we determined that the PI3K pathway regulates cry expression in GB cells, and in turn, cry is necessary and sufficient to promote Myc accumulation in GB. These results contribute to understanding the mechanisms underlying GB malignancy and lethality, and describe a novel role of Cry in GB cells.

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Section: Discussionmentioning

confidence: 99%

Circadian Gene cry Controls Tumorigenesis through Modulation of Myc Accumulation in Glioblastoma Cells

Jarabo¹,

Pablo²,

González-Blanco³

et al. 2022

IJMS

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“…Different studies have established a relation between alterations in circadian rhythm genes and cancer. Specifically, one of the genes associated with different types of cancer is cry (Shafi et al 2021;Yang et al 2021;Mampay et al 2021). So this study aims to investigate the role of cry in a Drosophila GB model.…”

Section: Discussionmentioning

confidence: 99%

Circadian Gene <em>cry</em> Controls Glioblastoma Tumorigenesis through Modulation of <em>myc</em> Expression

Jarabo¹,

Pablo²,

González-Blanco³

et al. 2021

Preprint

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Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. It is a very aggressive tumor that grows fast and spreads through the brain causing the death of patients in 15 months. GB cells mutate frequently and generate a heterogeneous population of tumoral cells genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We use a Drosophila model of GB that reproduces the features of human GB, and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We study the contribution of cry to the expansion of GB cells, to the neurodegeneration caused by GB, and to premature death and determine that cry is required for GB progression. Moreover, we analyze the mechanisms that regulate cry expression by the PI3K pathway. Finally, we conclude that cry is necessary and sufficient to regulate myc expression in GB. These results contribute to the understanding of the signals that impulse GB malignancy and lethality and open novel opportunities for the treatment of GB patients.

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“…Among TME processes, the circadian clock operates on immune escape and angiogenesis. The effect of the circadian clock on tumor progression is probably dependent on its effects on stem cells and the pro-tumor TME [ 81 , 82 ].…”

Section: The Tumor Microenvironment: the Role Of Cscs And Cooperative Cellsmentioning

confidence: 99%

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Meldolesi

2022

IJMS

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Stem cells, identified several decades ago, started to attract interest at the end of the nineties when families of mesenchymal stem cells (MSCs), concentrated in the stroma of most organs, were found to participate in the therapy of many diseases. In cancer, however, stem cells of high importance are specific to another family, the cancer stem cells (CSCs). This comprehensive review is focused on the role and the mechanisms of CSCs and of their specific extracellular vesicles (EVs), which are composed of both exosomes and ectosomes. Compared to non-stem (normal) cancer cells, CSCs exist in small populations that are preferentially distributed to the niches, such as minor specific tissue sites corresponding to the stroma of non-cancer tissues. At niches and marginal sites of other cancer masses, the tissue exhibits peculiar properties that are typical of the tumor microenvironment (TME) of cancers. The extracellular matrix (ECM) includes components different from non-cancer tissues. CSCs and their EVs, in addition to effects analogous to those of MSCs/EVs, participate in processes of key importance, specific to cancer: generation of distinct cell subtypes, proliferation, differentiation, progression, formation of metastases, immune and therapy resistance, cancer relapse. Many of these, and other, effects require CSC cooperation with surrounding cells, especially MSCs. Filtered non-cancer cells, especially macrophages and fibroblasts, contribute to collaborative cancer transition/integration processes. Therapy developments are mentioned as ongoing preclinical initiatives. The preliminary state of clinical medicine is presented in terms of both industrial development and future treatments. The latter will be administered to specific patients together with known drugs, with the aim of eradicating their tumor growth and metastases.

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Circadian clock, carcinogenesis, chronochemotherapy connections

Cited by 45 publications

References 106 publications

Circadian Gene cry Controls Tumorigenesis through Modulation of Myc Accumulation in Glioblastoma Cells

Circadian Gene cry Controls Tumorigenesis through Modulation of Myc Accumulation in Glioblastoma Cells

Circadian Gene <em>cry</em> Controls Glioblastoma Tumorigenesis through Modulation of <em>myc</em> Expression

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

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