Common BRAF(V600E)-directed pathway mediates widespread epigenetic silencing in colorectal cancer and melanoma

Proceedings of the National Academy of Sciences of the United States of America
Minggang FangM R Green

Abstract

During cancer development, it is well established that many genes, including tumor suppressor genes, are hypermethylated and transcriptionally repressed, a phenomenon referred to as epigenetic silencing. In general, the factors involved in, and the mechanistic basis of, epigenetic silencing during cancer development are not well understood. We have recently described an epigenetic silencing pathway, directed by the oncogenic B-Raf proto-oncogene (BRAF) variant BRAF(V600E), that mediates widespread epigenetic silencing in colorectal cancer (CRC). Notably, the BRAF(V600E) mutation is also present in 50-70% of melanomas. Here, we show that the same pathway we identified in CRC also directs epigenetic silencing of a similar set of genes in BRAF-positive melanoma. In both CRC and melanoma, BRAF(V600E) promotes epigenetic silencing through up-regulation of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG), a transcriptional repressor with sequence-specific DNA-binding activity. The elevated concentration of MAFG drives DNA binding on the promoter. Promoter-bound MAFG recruits a set of corepressors that includes its heterodimeric partner BTB and CNC homology 1, basic leucine zipper transcription factor 1 (BACH1), t...Continue Reading

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Citations

Mar 15, 2016·Cancer Letters·Yoshifumi BabaHideo Baba
Nov 3, 2016·Therapeutic Advances in Gastroenterology·Marina De RosaPaolo Delrio
Apr 12, 2017·Clinical Epigenetics·Goran MicevicMarcus Bosenberg
Sep 25, 2017·International Journal of Cancer. Journal International Du Cancer·Christopher KorchAmanda Capes-Davis
Oct 5, 2019·Cancers·Mehwish Khaliq, Mohammad Fallahi-Sichani
Jun 5, 2020·Antioxidants·Álvaro García-GuedeInmaculada Ibáñez-de-Caceres
Jun 26, 2020·Journal of Pathology and Translational Medicine·Jung Ho Kim, Gyeong Hoon Kang
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Oct 30, 2018·Oxidative Medicine and Cellular Longevity·Xinyue ZhangDan Meng
Mar 2, 2017·International Journal of Genomics·Pan ZhangYan Guo
Jan 2, 2019·Gastroenterology Research and Practice·Catherine E Bond, Vicki L J Whitehall
Aug 23, 2020·Cancers·Federica MarmorinoChiara Cremolini
Jan 30, 2019·Frontiers in Molecular Neuroscience·A Ayanna WadeAlex S Nord
Nov 18, 2018·Clinical Epigenetics·Stefano AmatoriMirco Fanelli
Apr 4, 2021·Cells·Joselyn Padilla, Jiyoung Lee
Apr 4, 2021·Cancers·Olga VeraFlorian A Karreth
Apr 4, 2021·International Journal of Molecular Sciences·Margaret Ottaviano On Behalf Of Scito Youth
Jun 3, 2021·International Journal of Molecular Sciences·Stephanie McKenna, Lucía García-Gutiérrez
Aug 3, 2021·The Journal of Biological Chemistry·Kazuhiko IgarashiMitsuyo Matsumoto

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