Epigenetics in cancer stem cells

Toh, Tan Boon; Lim, Jackwee; Chow, Edward K.

doi:10.1186/s12943-017-0596-9

Cited by 349 publications

(266 citation statements)

References 301 publications

(251 reference statements)

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“…Chromatin structure defines the state in which genetic information in the form of DNA is organized (Toh et al, 2017). Recent advances in cancer research have shown that global changes in the epigenetic landscape are a hallmark of various types of malignant diseases, including prostate cancer (PCa) (Jeronimo et al, 2011;Baylin, 2002, 2007).…”

Section: Introductionmentioning

confidence: 99%

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis

et al. 2019

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DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer ( PC a). Several studies have delineated sarcosine as a PC a oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N‐demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl‐donor S ‐adenosylmethionine ( SAM e), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5‐azacytidine, which was able to inhibit sarcosine‐induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAM e and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.

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Section: Introductionmentioning

confidence: 99%

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis

et al. 2019

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“…27 As a pluripotent transcription factor, SOX2 is expressed in CSCs of many types of tumors to induce and maintain their pluripotency and tumorigenic ability. 28 Recently, it is also reported to be required for the initiation and growth of melanoma CSCs. 16 Here, we demonstrate that SOX2 is also sufficient and necessary for the induction of melanoma SP cells.…”

Section: Discussionmentioning

confidence: 99%

SOX2 upregulates side population cells and enhances their chemoresistant ability by transactivating ABCC1 expression contributing to intrinsic resistance to paclitaxel in melanoma

Gao

2019

Molecular Carcinogenesis

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Paclitaxel is the last choice for the treatment of advanced melanoma as a second‐line chemotherapeutic agent, but there are still many cases of intrinsic resistance to paclitaxel in melanoma and the reasons that cause paclitaxel resistance remain unclear. Here, we identified that high expression of SRY‐box transcription factor 2 (SOX2) and high ratio of side population (SP) cells reduced the sensitivity to paclitaxel in melanoma cells. The knockout and the induction of SOX2 completely depleted and significantly upregulated the ratios of melanoma SP cells, respectively. These data suggest that SOX2, a pluripotent transcription factor for inducing cancer stem cells in melanoma, is also sufficient and necessary for the induction of melanoma SP cells. ATP‐binding cassette (ABC) subfamily C member 1 (ABCC1) is one of ABC transporters which causes SP cells to be resistance to chemotherapeutic agents by efficiently pumping drugs out of cells. The knockout and the induction of ABCC1 significantly increased and decreased the sensitivity of melanoma cells to paclitaxel. High expression of ABCC1 was identified in melanoma cell lines with high expression of SOX2 and in their SP cells. SOX2 was identified to induce ABCC1 transcription. Taken together, SOX2 upregulates SP cells and enhances their chemoresistant ability by increasing ABCC1 expression, which contributes to intrinsic resistance to paclitaxel in melanoma. Our findings will lead to new insights into melanoma biology and therapy resistance, and eventually to new therapeutic targets.

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“…More understanding about these signaling pathways could contribute to the design and development of new therapeutic platforms. In this context, epigenetic regulations appeared as key modulators in cancer and CSCs [65][66][67][68][69][70]. MicroRNAs (miRNAs) are one of main epigenetic regulators which act as oncogenes or tumor suppressors [71][72][73][74][75][76][77][78].…”

Section: Diagnosis and Treatment Of Pcmentioning

confidence: 99%

Cancer stem cells as therapeutic targets of pancreatic cancer

Razi

Radak

Mahjoubin‐Tehran

et al. 2019

Fundamemntal Clinical Pharma

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The discovery of stem cells and their potential abilities in self‐renewal and differentiation has opened a new horizon in medicine. Scientists have found a small population of stem cells in some types of cancers with the same functions as normal stem cells. There are two models for tumor progression: clonal (stochastic) and cancer stem cell (CSCs) models. According to the first model, all transformed cells in the tumor have carcinogenic potential and are able to proliferate and produce the same cells. The latter model, which has received more attention recently, considers the role of CSCs in drug resistance and tumor metastasis. Following the model, researchers have found that targeting CSCs may be a promising way in cancer therapy. This review describes CSC characteristics in general, while also focusing on CSC properties in the context of pancreatic cancer.

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Epigenetics in cancer stem cells

Cited by 349 publications

References 301 publications

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis

Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis

SOX2 upregulates side population cells and enhances their chemoresistant ability by transactivating ABCC1 expression contributing to intrinsic resistance to paclitaxel in melanoma

Cancer stem cells as therapeutic targets of pancreatic cancer

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