Histone modifications as a pathogenic mechanism of colorectal tumorigenesis

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• 作者：Antonios N. Gargalionis¹ ; Christina Piperi¹ ; Christos Adamopoulos ; Athanasios G. Papavassiliou ; ^{papavas@med.uoa.gr} ; ^{gpapavas@ath.forthnet.gr}
• 关键词：AP2A1 ; adaptor related protein complex 2 ; subunit alpha 1 ; APAF1 ; apoptotic protease activating factor 1 ; APC ; adenomatous polyposis coli ; BRCA1 ; 2 ; breast cancer 1 ; 2 ; CARM1 ; co-activator-associated arginine methyltransferase 1 ; CBP ; cAMP-responsive elem
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2012
• 期刊代码：127_13572725
• 类别：med
• 出版时间：August, 2012
• 卷：44
• 期：8
• 页码：1276-1289
• 文件大小：1323 K

摘要

Epigenetic regulation of gene expression has provided colorectal cancer (CRC) pathogenesis with an additional trait during the past decade. In particular, histone post-translational modifications set up a major component of this process dictating chromatin status and recruiting non-histone proteins in complexes formed to 鈥渉andle DNA鈥? In CRC, histone marks of aberrant acetylation and methylation levels on specific residues have been revealed, along with a plethora of deregulated enzymes that catalyze these reactions. Mutations, deletions or altered expression patterns transform the function of several histone-modifying proteins, further supporting the crucial role of epigenetic effectors in CRC oncogenesis, being closely associated to inactivation of tumor suppressor genes. Elucidation of the biochemical basis of these new tumorigenic mechanisms allows novel potential prognostic factors to come into play. Moreover, the detection of these changes even in early stages of the multistep CRC process, along with the reversible nature of these mechanisms and the technical capability to detect such alterations in cancer cells, places this group of covalent modifications as a further potential asset for clinical diagnosis or treatment of CRC. This review underlines the biochemistry of histone modifications and the potential regulatory role of histone-modifying proteins in CRC pathogenesis, to date. Furthermore, the underlying mechanisms of the emerging epigenetic interplay along with the chemical compounds that are candidates for clinical use are discussed, offering new insights for further investigation of key histone enzymes and new therapeutic targets.