American Journal of Cancer Prevention
ISSN (Print): 2328-7314 ISSN (Online): 2328-7322 Website: Editor-in-chief: Nabil Abdel-Hamid
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American Journal of Cancer Prevention. 2020, 8(1), 7-12
DOI: 10.12691/ajcp-8-1-2
Open AccessArticle

Histone Acetylation Modification H4K16ac Involved in Notch1 Signaling in Breast Cancer

Ya-qi Wang1, , Jing-hua Zhang2, , Zhao-yuan Wan3 and Dan Li3

1Department of Surgical Oncology, Tangshan People's Hospital, Tangshan, China

2Department of Surgical, Tangshan Women and Children's Hospital, Tangshan, China

3Cancer Institute, Tangshan People’s Hospital, Tangshan, China

Pub. Date: December 11, 2020

Cite this paper:
Ya-qi Wang, Jing-hua Zhang, Zhao-yuan Wan and Dan Li. Histone Acetylation Modification H4K16ac Involved in Notch1 Signaling in Breast Cancer. American Journal of Cancer Prevention. 2020; 8(1):7-12. doi: 10.12691/ajcp-8-1-2


The Notch signaling pathway is a fundamental intercellular signaling system that regulates cell fate decisions in terms of proliferation and differentiation in multiple tissues. Abnormal activation of Notch1 signaling pathway leads to a variety of diseases, including the malignant tumors. Dysregulated Notch receptor activity has been implicated in breast cancer but the epigenetic mechanisms remains not clear. Compared to adjacent tissues, high expression of NIC1 and low expression of H4K16ac were found in cancer tissues. Notch1 knocked down in the breast cancer cell line MCF-7 resulted in increased H4K16ac expression and a parallel reduction in their proliferation and migration capacity. Our study prompting H4K16ac to participate in the signal transduction of Notch1 in breast cancer cells. These results confirm Notch1 as a signal triggering epigenetic mechanisms in breast cancer cells, which may have implications in tumor dissemination, metastasis and proliferation. The identification of specific factors interacting with NOTCH signaling could thus be relevant to fully understanding the role of NOTCH in breast neoplasia.

breast cancer notch1 signaling in tumorigenesis epigenetic modification H4K16ac

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[1]  Amir, Qaseem, Jennifer, et al. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians [J]. 2019,
[2]  Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China [J]. 2014, 15(7): e279-e89.
[3]  Bao, Bin, Wang, et al. Notch-1 induces Epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells (Retraction of Vol 307, Pg 26, 2011) [J]. 2018,
[4]  Sandra H, Michael P, Beate GJJon. Notch signaling [J]. 2018, 2007, 107 (5): 1060-1; author reply 1-2.
[5]  Kadian LK, Gulshan G, Ahuja P, et al. Aberrant promoter methylation of NOTCH1 and NOTCH3 and its association with cervical cancer risk factors in North Indian population [J]. 2020, 12(6):
[6]  Struhl, Dev KJG. Histone acetylation and transcriptional regulatorymechanisms [J]. 1998, 12(5): 599-606.
[7]  Grunstein, Nature MJ. Histone acetylation in chromatin structure and transcription [J]. 1997.
[8]  Guo P, Chen W, Li H, et al. The Histone Acetylation Modifications of Breast Cancer and their Therapeutic Implications [J]. 2018, 24(1-7).
[9]  Damien N, Benjamin Z, Suter DM, et al. Modulation of transcriptional burst frequency by histone acetylation [J]. 2018, 115(7153).
[10]  A YN, A YY, A JR, et al. miR-15a-5p inhibits metastasis and lipid metabolism by suppressing histone acetylation in lung cancer [J]. 2020, 161(150-62).
[11]  Senapati P, Kato H, Lee M, et al. Hyperinsulinemia promotes aberrant histone acetylation in triple-negative breast cancer [J]. 2019, 12(1).
[12]  Nizovtseva EV, Gerasimova NS, Studitsky VMJMUBSB. Effect of Acetylation of Histone H4 on Communication in Chromatin [J]. 2019, 74(4): 246-9.
[13]  Huang TH, Shen ZJ, Sleckman BP, et al. The histone chaperone ASF1 regulates the activation of ATM and DNA-PKcs in response to DNA double-strand breaks [J]. 2018, 15384101.2018.1486165.
[14]  Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment %J Nucleic Acids Research [J]. 2019, 10): 10.
[15]  Yan L, Xing ZB, Wang SQ, et al. MDM2–MOF–H4K16ac axis contributes to tumorigenesis induced by Notch [J]. 2014, 281.
[16]  Li C, He X, Huang Z, et al. Melatonin ameliorates the advanced maternal age-associated meiotic defects in oocytes through the SIRT2-dependent H4K16 deacetylation pathway [J]. 2020, 12(2): 1610-23.
[17]  Zhong J, Ji L, Chen H, et al. Acetylation of hMOF Modulates H4K16ac to Regulate DNA Repair Genes in Response to Oxidative Stress [J]. 2017, 13(7): 923-34.
[18]  Yan, Liu, Yue-Hong, et al. JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity [J]. 2018,
[19]  Nei MJAN. Genetic Distance between Populations [J]. 1972, 106(949): 283-92.
[20]  Wang, Therapeutics ZJMC. Down-regulation of Notch-1 contributes to cell growth inhibition and apoptosis in pancreatic cancer cells [J]. 2006, 5(3): 483-93.
[21]  Anna B, Lluis EJCOiCB. The multiple usages of Notch signaling in development, cell differentiation and cancer [J]. 2018, 55(1-7).
[22]  Koch U, Radtke FJC, Cmls MLS. Notch and cancer: a double-edged sword [J]. 2007, 64(21): 2746-62.
[23]  Bolós V, Grego-Bessa J, Luis DLP, José %J Endocrine Reviews. Notch signaling in development and cancer [J]. 2007, 28(3): 339-63.
[24]  Cho S, Lu M, He X, et al. Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells [J]. 2011, 108(51): 20778-83.
[25]  Robert K, Tremblay I, Boucher MJJP. The intracellular domain of Notch1 (NIC1) is hyperphosphorylated following its activation in human pancreatic cancer cells [J]. 2013, 13(2): e68.
[26]  Chu J, Jeffries S, Norton JE, et al. Repression of Activator Protein-1-mediated Transcriptional Activation by the Notch-1 Intracellular Domain [J]. 2002, 277(9): 7587-97.
[27]  Zhang J, Yu K, Han X, et al. Paeoniflorin influences breast cancer cell proliferation and invasion via inhibition of the Notch1 signaling pathway [J]. 2018,
[28]  Li S, Huang C, Hu G, et al. Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals [J]. 2020, 11(3):
[29]  Masuda SJAoO. Notch1 and Notch2 have opposite prognostic effects on patients with colorectal cancer [J]. 2011,
[30]  Sharma A, Paranjape AN, Rangarajan A, et al. A Monoclonal Antibody against Human Notch1 Ligand-Binding Domain Depletes Subpopulation of Putative Breast Cancer Stem-like Cells [J]. 2011.
[31]  Lin, Zhu, Jiaxing, et al. Expression of hMOF, but not HDAC4, is responsible for the global histone H4K16 acetylation in gastric carcinoma [J]. 2015.