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The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer

2015; Wiley; Volume: 42; Issue: 5 Linguagem: Inglês

10.1111/1440-1681.12382

1440-1681

Muyang Ding, Hang Zhang, Zhen Li, Cuili Wang, Jasmine Chen, Liyun Shi, Dakang Xu, Yane Gao,

Cancer-related gene regulation

Summary Enhancer of zeste 2 ( EZH 2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH 2 is associated with cervical cancer progression, particularly the progression to invasive squamous cell carcinoma. Enhancer of zeste 2 is known to trimethylate lysine 27 on histone H3, leading to gene silencing that contributes to the progression of tumours into a more aggressive form of cancer. However, the specific molecular mechanisms by which EZH 2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH 2 inhibitor was reported to selectively inhibit trimethylated lysine 27 on histone H3 and to reactivate silenced genes in cancer cells. In this study, we found that GSK 343 (a specific inhibitor of EZH 2 methyltransferase) induces phenotypic reprogramming of cancer cells from mesenchymal to epithelial cells, reducing proliferation and cell motility and blocking the invasion of cervical cancer cell lines both in vitro and in vivo . Treatment with the EZH 2 inhibitor led to increased levels of the epithelial marker E‐cadherin and decreased levels of mesenchymal markers such as N‐cadherin and vimentin. The observed reprogramming is associated with restrained cervical cancer progression and provides direct evidence in support of EZH 2 as a therapeutic target.