المؤلفون: Moscona, Roy, Janssen, Sanne Marlijn, Elchebly, Mounib, Papadakis, Andreas Ioannis, Rubin, Eitan, Spatz, Alan

المصدر: Pigment Cell & Melanoma Research; May-Jul2023, Vol. 36 Issue 3/4, p299-313, 15p

مصطلحات موضوعية: TUMOR suppressor genes, CHROMATIN, MELANOMA, GENE expression, GENETIC regulation, SKIN cancer

مستخلص: Melanoma is the deadliest form of skin cancer, due to its tendency to metastasize early. Brother of regulator of imprinted sites (BORIS), also known as CCCTC binding factor-like (CTCFL), is a transcription regulator that becomes ectopically expressed in melanoma. We recently showed that BORIS contributes to melanoma phenotype switching by altering the gene expression program of melanoma cells from an intermediate melanocytic state toward a more mesenchymal-like state. However, the mechanism underlying this transcriptional switch remains unclear. Here, ATAC-seq was used to study BORIS-mediated chromatin accessibility alterations in melanoma cells harboring an intermediate melanocytic state. The gene set that gained promoter accessibility, following ectopic BORIS expression, showed enrichment for biological processes associated with melanoma invasion, while promoters of genes associated with proliferation showed reduced accessibility. Integration of ATAC-seq and RNA-seq data demonstrated that increased chromatin accessibility was associated with transcriptional upregulation of genes involved in tumor progression processes, and the aberrant activation of oncogenic transcription factors, while reduced chromatin accessibility and downregulated genes were associated with repressed activity of tumor suppressors and proliferation factors. Together, these findings indicate that BORIS mediates transcriptional reprogramming in melanoma cells by altering chromatin accessibility and gene expression, shifting the cellular transcription landscape of melanoma cells toward a mesenchymal-like genetic signature. [ABSTRACT FROM AUTHOR]

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المؤلفون: Redpath, Margaret, Xu, Bin, van Kempen, Leon C, Spatz, Alan

المصدر: Redpath , M , Xu , B , van Kempen , L C & Spatz , A 2011 , ' The dual role of the X-linked FoxP3 gene in human cancers ' , Molecular oncology , vol. 5 , no. 2 , pp. 156-63 . https://doi.org/10.1016/j.molonc.2011.03.001Test

مصطلحات موضوعية: Animals, Forkhead Transcription Factors/genetics, Gene Expression Regulation, Neoplastic, Humans, Melanoma/genetics, Neoplasms/genetics, Skin Neoplasms/genetics

الوصف: The FoxP3 (forkhead box P3) gene is an X-linked gene that is submitted to inactivation. It is an essential transcription factor in CD4(+)CD25(+)FoxP3 regulatory T cells, which are therapeutic targets in disseminated cutaneous melanoma. Moreover, FoxP3 is an important tumor suppressor gene in carcinomas and has putative cancer suppressor gene function in cutaneous melanoma as well. Therefore understanding the structure and function of the FoxP3 gene is crucial to gaining insight into the biology of melanoma to better develop immunotherapeutics and future therapeutic strategies.

وصف الملف: application/pdf

العلاقة: https://research.rug.nl/en/publications/f671c2ec-58c5-4913-9021-c67f2abe0058Test

الإتاحة: https://doi.org/10.1016/j.molonc.2011.03.001Test
https://hdl.handle.net/11370/f671c2ec-58c5-4913-9021-c67f2abe0058Test
https://research.rug.nl/en/publications/f671c2ec-58c5-4913-9021-c67f2abe0058Test
https://pure.rug.nl/ws/files/121822760/The_dual_role_of_the_X_linked_FoxP3_gene_in_human_cancers.pdfTest

المؤلفون: van Kempen, Léon C L, Redpath, Margaret, Elchebly, Mounib, Klein, Kathleen Oros, Papadakis, Andreas I, Wilmott, James S, Scolyer, Richard A, Edqvist, Per-Henrik, Pontén, Fredrik, Schadendorf, Dirk, van Rijk, Anke F, Michiels, Stefan, Dumay, Anne, Helbling-Leclerc, Anne, Dessen, Philippe, Wouters, Jasper, Stass, Marguerite, Greenwood, Celia M T, Ghanem, Ghanem E, van den Oord, Joost, Feunteun, Jean, Spatz, Alan

المصدر: van Kempen , L C L , Redpath , M , Elchebly , M , Klein , K O , Papadakis , A I , Wilmott , J S , Scolyer , R A , Edqvist , P-H , Pontén , F , Schadendorf , D , van Rijk , A F , Michiels , S , Dumay , A , Helbling-Leclerc , A , Dessen , P , Wouters , J , Stass , M , Greenwood , C M T , Ghanem , G E , van den Oord , J , Feunteun , J & Spatz ....

مصطلحات موضوعية: Animals, Cell Cycle Proteins/genetics, Cell Line, Tumor, Chromosome Aberrations, Chromosomes, Human, DNA Replication, Disease Progression, Disease-Free Survival, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, HEK293 Cells, Humans, Male, Melanoma/genetics, Mice, Neoplasm Metastasis, Neoplasm Transplantation, Nuclear Proteins/metabolism, Prognosis, Protein Phosphatase 2/genetics, Sex Factors, Skin Neoplasms/metabolism

الوصف: Male gender is independently and significantly associated with poor prognosis in melanoma of all clinical stages. The biological underpinnings of this sex difference remain largely unknown, but we hypothesized that gene expression from gonosomes (sex chromosomes) might play an important role. We demonstrate that loss of the inactivated X chromosome in melanomas arising in females is strongly associated with poor distant metastasis-free survival, suggesting a dosage benefit from two X chromosomes. The gonosomal protein phosphatase 2 regulatory subunit B, beta (PPP2R3B) gene is located on the pseudoautosomal region (PAR) of the X chromosome in females and the Y chromosome in males. We observed that, despite its location on the PAR that predicts equal dosage across genders, PPP2R3B expression was lower in males than in females and was independently correlated with poor clinical outcome. PPP2R3B codes for the PR70 protein, a regulatory substrate-recognizing subunit of protein phosphatase 2A. PR70 decreased melanoma growth by negatively interfering with DNA replication and cell cycle progression through its role in stabilizing the cell division cycle 6 (CDC6)-chromatin licensing and DNA replication factor 1 (CDT1) interaction, which delays the firing of origins of DNA replication. Hence, PR70 functionally behaves as an X-linked tumor suppressor gene.

الإتاحة: https://doi.org/10.1126/scitranslmed.aai9188Test
http://hdl.handle.net/11370/d2bc7fba-e07b-4524-b202-f741086ee033Test
https://research.rug.nl/en/publications/the-protein-phosphatase-2a-regulatory-subunit-pr70-is-a-gonosomal-melanoma-tumor-suppressor-geneTest(d2bc7fba-e07b-4524-b202-f741086ee033).html