NDLI: EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis

Content Provider	Springer Nature Link
Author	Crea, Francesco Fornaro, Lorenzo Bocci, Guido Sun, Lei Farrar, William L. Falcone, Alfredo Danesi, Roma
Copyright Year	2012
Abstract	Tumor angiogenesis and metastatic spreading are two highly interconnected phenomena, which contribute to cancer-associated deaths. Thus, the identification of novel strategies to target angiogenesis and metastatic spreading is crucial. Polycomb genes are a set of epigenetic effectors, structured in multimeric repressive complexes. EZH2 is the catalytic subunit of Polycomb repressive complex 2 (PRC2), which methylates histone H3 lysine 27, thereby silencing several tumor-suppressor genes. EZH2 is essential for cancer stem cell self-renewal. Interestingly, cancer stem cells are thought to be the seeds of metastatic spreading and are able to differentiate into tumor-associated endothelial cells. Pre-clinical studies showed that EZH2 is able to silence several anti-metastatic genes ( e.g., E-cadherin and tissue inhibitors of metalloproteinases), thereby favoring cell invasion and anchorage-independent growth. In addition, EZH2 seems to play a crucial role in the regulation of tumor angiogenesis. High EZH2 expression predicts poor prognosis, high grade, and high stage in several cancer types. Recently, a small molecule inhibitor of PRC2 (DZNeP) demonstrated promising anti-tumor activity, both in vitro and in vivo. Interestingly, DZNeP was able to inhibit cancer cell invasion and tumor angiogenesis in prostate and brain cancers, respectively. At tumor-inhibiting doses, DZNeP is not harmful for non-transformed cells. In the present manuscript, we review current evidence supporting a role of EZH2 in metastatic spreading and tumor angiogenesis. Using Oncomine datasets, we show that DZNeP targets are specifically silenced in some metastatic cancers, and some of them may inhibit angiogenesis. Based on this evidence, we propose the development of EZH2 inhibitors as anti-angiogenic and anti-metastatic therapy.
Starting Page	753
Ending Page	761
Page Count	9
File Format	PDF
ISSN	01677659
Journal	Cancer and Metastasis Reviews
Volume Number	31
Issue Number	3-4
e-ISSN	15737233
Language	English
Publisher	Springer US
Publisher Date	2012-06-19
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	EZH2 Metastasis Angiogenesis DZNeP Polycomb Biomedicine general Oncology Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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