Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells

Zhang, Zan1,2; Lei, Anhua1,2; Xu, Liyang1,2; Chen, Lu1,2; Chen, Yonglong3; Zhang, Xuena1,2; Gao, Yan1,2; Yang, Xiaoli1,2; Zhang, Min1,2; Cao, Ying1,2

2017-08-04

10.1074/jbc.M117.785865

JOURNAL OF BIOLOGICAL CHEMISTRY   影响因子和分区

0021-9258

1083-351X

Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines. The regulatory effect of these enzymes in neuronal differentiation resided in their intrinsic activity in embryonic neural precursor/progenitor cells. We further found that a major part of pan-cancer-promoting genes and the signal transducers of the pan-cancer-promoting signaling pathways, including the epithelial-to-mesenchymal transition (EMT) mesenchymal marker genes, display neural specific expression during embryonic neurulation. In contrast, many tumor suppressor genes, including the EMT epithelial marker gene that encodes cadherin 1 (CDH1), exhibited non-neural or no expression. This correlation indicated that cancer cells and embryonic neural cells share a regulatory network, mediating both tumorigenesis and neural development. This observed similarity in regulatory mechanisms suggests that cancer cells might share characteristics of embryonic neural cells.

cell differentiation embryo gene expression neurodevelopment neurodifferentiation Xenopus cancer cell lines chromatin modification factors embryonic neural precursor cells

SCI ; EI

英语

NI论文

其他

Shenzhen Science and Technology Innovation Commission Grant[JCYJ20150331101823697]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000407220100015

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

20173204022994

Amino acids ; Cell culture ; Enzyme inhibition ; Gene expression

Biological Materials and Tissue Engineering:461.2 ; Organic Compounds:804.1

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Nanjing Univ, Model Anim Res Ctr, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China
2.MOE Key Lab Model Anim Dis Study, 12 Xuefu Rd, Nanjing 210061, Jiangsu, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Key Lab Cell Microenvironm, Dept Biol, Shenzhen 518055, Guangdong, Peoples R China

Zhang, Zan,Lei, Anhua,Xu, Liyang,et al. Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(31):12842-12859.

Zhang, Zan.,Lei, Anhua.,Xu, Liyang.,Chen, Lu.,Chen, Yonglong.,...&Cao, Ying.(2017).Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells.JOURNAL OF BIOLOGICAL CHEMISTRY,292(31),12842-12859.

Zhang, Zan,et al."Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells".JOURNAL OF BIOLOGICAL CHEMISTRY 292.31(2017):12842-12859.