Methyltransferases in the Pathogenesis of Keratinocyte Cancers

Ko, Eun Kyung; Capell, Brian C.

doi:10.3390/cancers13143402

Cited by 5 publications

(2 citation statements)

References 113 publications

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“…Consistent with this, the depletion of DNMT1 in human epidermal stem cells (EpSC) promotes premature, irreversible differentiation. DNMT3A and DNMT3B play important roles in regulating human EpSC homeostasis via their ability to promote enhancer activity of genes involved in self-renewal and differentiation [63]. For what concerns the expression of DNA demethylases, we noticed a general downregulation of their level in vaginal keratinocytes after discontinuous PE N/MPL exposure.…”

Section: Discussionmentioning

confidence: 80%

Assessing the Impact of Polyethylene Nano/Microplastic Exposure on Human Vaginal Keratinocytes

Pontecorvi,

Ceccarelli,

Cece

et al. 2023

IJMS

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The global rise of single-use throw-away plastic products has elicited a massive increase in the nano/microplastics (N/MPLs) exposure burden in humans. Recently, it has been demonstrated that disposable period products may release N/MPLs with usage, which represents a potential threat to women’s health which has not been scientifically addressed yet. By using polyethyl ene (PE) particles (200 nm to 9 μm), we showed that acute exposure to a high concentration of N/MPLs induced cell toxicity in vaginal keratinocytes after effective cellular uptake, as viability and apoptosis data suggest, along with transmission electron microscopy (TEM) observations. The internalised N/MPLs altered the expression of junctional and adherence proteins and the organisation of the actin cortex, influencing the level of genes involved in oxidative stress signalling pathways and that of miRNAs related to epithelial barrier function. When the exposure to PE N/MPLs was discontinued or became chronic, cells were able to recover from the negative effects on viability and differentiation/proliferation gene expression in a few days. However, in all cases, PE N/MPL exposure prompted a sustained alteration of DNA methyltransferase and DNA demethylase expression, which might impact epigenetic regulation processes, leading to accelerated cell ageing and inflammation, or the occurrence of malignant transformation.

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Section: Discussionmentioning

confidence: 80%

Assessing the Impact of Polyethylene Nano/Microplastic Exposure on Human Vaginal Keratinocytes

Pontecorvi,

Ceccarelli,

Cece

et al. 2023

IJMS

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“…Finally, mutations in chromatin-modifying enzymes, leading to DNA and histone modifications, have been described in cancer. In this sense, loss-of-function mutations in the H3K4 methyltransferases, KMT2C, and KMT2D have been described in CSCC [ 49 ]. Additionally, inactivating mutations have been reported in the lysine demethylase 6A (KDM6A) in HNSCC [ 27 , 28 , 29 ].…”

Section: The Process Of Carcinogenesis: Gene Mutations In Oral and Cu...mentioning

confidence: 99%

The Distinctive Features behind the Aggressiveness of Oral and Cutaneous Squamous Cell Carcinomas

Alonso-Juarranz

Mascaraque

Carrasco

et al. 2023

Cancers

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Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in TP53 (encoding pP53 protein), CDKN2A (encoding cyclin dependent kinase inhibitor 2A), FAT1 (encoding FAT atypical cadherin 1), and KMT2D (encoding lysine methyltransferase 2D), with the exception of NOTCH (encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.

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