Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis

Abstract

Metastasis is a complex process that involved in various genetic and epigenetic alterations during the progression of breast cancer. Recent evidences have indicated that the mutation in the genome sequence may not be the key factor for increasing metastatic potential. Epigenetic changes were revealed to be important for metastatic phenotypes transition with the development in understanding the epigenetic basis of breast cancer. Herein, we aim to present the potential epigenetic drivers that induce dysregulation of genes related to breast tumor growth and metastasis, with a particular focus on histone modification including histone acetylation and methylation. The pervasive role of major histone modification enzymes in cancer metastasis such as histone acetyltransferases (HAT), histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and so on are demonstrated and further discussed. In addition, we summarize the recent advances of next-generation sequencing technologies and microfluidic-based devices for enhancing the study of epigenomic landscapes of breast cancer. This feature also introduces several important biotechnologists for identifying robust epigenetic biomarkers and enabling the translation of epigenetic analyses to the clinic. In summary, a comprehensive understanding of epigenetic determinants in metastasis will offer new insights of breast cancer progression and can be achieved in the near future with the development of innovative epigenomic mapping tools.

TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 Signaling Axis Promotes Viability, Migration, Invasion and EMT of Hepatocellular Carcinoma Cells

“… 24 As a developmental program, EMT has a critical function in metastasis, and in the process of metastatic progression, some modifications both genetic and epigenetic can endow malignant cells with the properties that have effects on modulation of metastatic capacity. 25 , 26 E-Cadherin, N-Cadherin, and Vimentin are those EMT-related factors. 27 As two members of the Cadherin family, E-Cadherin and N-Cadherin are the most prominent cell adhesion molecules, and E-Cadherin is a glycoprotein with transmembrane ability, which is pivotal to cell-to-cell adhesion and acts as tumor-suppressor, while N-Cadherin, on the opposite confers malignant cells upon metastasis acquisition or promotion.…”

Signaling pathways governing breast cancer stem cells behavior

“…Recently, studies have been suggested that epigenetic changes such as DNA methylation and histone modifications enhance the events of BCSC metastasis [126][127][128]. miRNAs are epigenetic modulators that target mRNAs without modifying the gene sequences [129,130].…”

Vitamin D endocrine system in breast cancer

“…This complex impacts transcription through interactions with histone acetyltransferases (HAT), followed by chromatin changes (Campbell et al, 2010). An increasing body of evidence reveals that histones' modifications (including methylation and acetylation) are involved in breast cancer metastasis (extensively reviewed in Nandy et al, 2020;Zhuang et al, 2020). According to Saramäki and others (Saramäki et al, 2009) both the histone acetylation and methylation processes are involved in cyclic chromatin looping during regulation of p21 expression after 1,25(OH) 2 D 3 supplementation to breast cancer cells.…”