The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer.
Enhancer of zeste 2 (EZH2), a polycomb histone methyltransferase, is overexpressed in various cancers, including cervical cancer. Gene expression analysis revealed that increased expression of EZH2 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 EZH2 contributes to the development of cervical cancer remain largely unknown. Recently, an EZH2 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 GSK343 (a specific inhibitor of EZH2 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 EZH2 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 EZH2 as a therapeutic target.
Department of Obstetrics and Gynecology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China.
Muyang
M
Ding
Hang
H
Zhang
Zhen
Z
Li
Cuili
C
Wang
Jasmine
J
Chen
Liyun
L
Shi
Dakang
D
Xu
Yane
Y
Gao
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007191:Indazoles / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011728:Pyridones / Q000494:pharmacology / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D015820:Cadherins; C586265:GSK343; D007191:Indazoles; D011728:Pyridones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
cervical cancer; enhancer of zeste 2 inhibitor; epithelial-mesenchymal transition; xenografts