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Beyond the histone tale: HP1? deregulation in breast cancer epigenetics.

ABSTRACT: Heterochromatin protein 1? (HP1?) encoded from the CBX5-gene is an evolutionary conserved protein that binds histone H3 di- or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures. HP1? has diverse functions in heterochromatin formation, gene regulation, and mitotic progression, and forms complex networks of gene, RNA, and protein interactions. Emerging evidence has shown that HP1? serves a unique biological role in breast cancer related processes and in particular for epigenetic control mechanisms involved in aberrant cell proliferation and metastasis. However, how HP1? deregulation plays dual mechanistic functions for cancer cell proliferation and metastasis suppression and the underlying cellular mechanisms are not yet comprehensively described. In this paper we provide an overview of the role of HP1? as a new sight of epigenetics in proliferation and metastasis of human breast cancer. This highlights the importance of addressing HP1? in breast cancer diagnostics and therapeutics.

SUBMITTER: Vad-Nielsen J

PROVIDER: S-EPMC4622548 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Beyond the histone tale: HP1α deregulation in breast cancer epigenetics.

Vad-Nielsen Johan J Nielsen Anders Lade AL

Cancer biology & therapy 20150101 2

Heterochromatin protein 1α (HP1α) encoded from the CBX5-gene is an evolutionary conserved protein that binds histone H3 di- or tri-methylated at position lysine 9 (H3K9me2/3), a hallmark for heterochromatin, and has an essential role in forming higher order chromatin structures. HP1α has diverse functions in heterochromatin formation, gene regulation, and mitotic progression, and forms complex networks of gene, RNA, and protein interactions. Emerging evidence has shown that HP1α serves a unique ...[more]

PMID: 25588111

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Project description:Dysregulated epigenetic enzymes and resultant abnormal epigenetic modifications (EMs) have been suggested to be closely related to tumor occurrence and progression. Histone modifications (HMs) can assist in maintaining genome stability, DNA repair, transcription, and chromatin modulation within breast cancer (BC) cells. In addition, HMs are reversible, dynamic processes involving the associations of different enzymes with molecular compounds. Abnormal HMs (e.g. histone methylation and histone acetylation) have been identified to be tightly related to BC occurrence and development, even though their underlying mechanisms remain largely unclear. EMs are reversible, and as a result, epigenetic enzymes have aroused wide attention as anti-tumor therapeutic targets. At present, treatments to restore aberrant EMs within BC cells have entered preclinical or clinical trials. In addition, no existing studies have comprehensively analyzed aberrant HMs within BC cells; in addition, HM-targeting BC treatments remain to be further investigated. Histone and non-histone protein methylation is becoming an attractive anti-tumor epigenetic therapeutic target; such methylation-related enzyme inhibitors are under development at present. Consequently, the present work focuses on summarizing relevant studies on HMs related to BC and the possible mechanisms associated with abnormal HMs. Additionally, we also aim to analyze existing therapeutic agents together with those drugs approved and tested through pre-clinical and clinical trials, to assess their roles in HMs. Moreover, epi-drugs that target HMT inhibitors and HDAC inhibitors should be tested in preclinical and clinical studies for the treatment of BC. Epi-drugs that target histone methylation (HMT inhibitors) and histone acetylation (HDAC inhibitors) have now entered clinical trials or are approved by the US Food and Drug Administration (FDA). Therefore, the review covers the difficulties in applying HM-targeting treatments in clinics and proposes feasible approaches for overcoming such difficulties and promoting their use in treating BC cases.

Dataset Information

Beyond the histone tale: HP1? deregulation in breast cancer epigenetics.

Publications

Beyond the histone tale: HP1α deregulation in breast cancer epigenetics.

Similar Datasets

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