G9a Is Essential for EMT-Mediated Metastasis and Maintenance of Cancer Stem Cell-Like Characters in Head and Neck Squamous Cell Carcinoma

Authors

Shuli Liu, Shanghai Jiao Tong University, China
Dongxia Ye, Shanghai Jiao Tong University, China
Wenzheng Guo, Shanghai Jiao Tong University, China
Wenwen Yu, Shanghai Jiao Tong University, China
Yue He, Shanghai Jiao Tong University, China
Jingzhou Hu, Shanghai Jiao Tong University, China
Yanan Wang, Shanghai Jiao Tong University, China
Ling Zhang, Shanghai Jiao Tong University, China
Yueling Liao, Shanghai Jiao Tong University, China
Hongyong Song, Shanghai Jiao Tong University, China
Shuangshuang Zhong, Shanghai Jiao Tong University, China
Dongliang Xu, Shanghai Jiao Tong University, China
Huijing Yin, Shanghai Jiao Tong University, China
Beibei Sun, Shanghai Jiao Tong University, China
Xiaofei Wang, Shanghai Jiao Tong University, China
Jingyi Liu, University of KentuckyFollow
Yadi Wu, University of KentuckyFollow
Binhua P. Zhou, University of KentuckyFollow
Zhiyuan Zhang, Shanghai Jiao Tong University, China
Jiong Deng, Shanghai Jiao Tong University, China

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 (H3K9). Moreover, G9a is required for both lymph node-related metastasis and TGF-β-induced EMT in HNSCC cells since knockdown of G9a reversed EMT, inhibited cell migration and tumorsphere formation, and suppressed the expression of CSC markers. Our study demonstrates that the G9a protein is essential for the induction of EMT and CSC-like properties in HNSCC. Thus, targeting the G9a-Snail axis may represent a novel strategy for treatment of metastatic HNSCC.

Document Type

Article

Publication Date

3-30-2015

Notes/Citation Information

Published in Oncotarget, v. 6, no. 9, p. 6887-6901.

Copyright @ 2008-2016 Impact Journals, LLC. All rights reserved.

Licensed under a Creative Commons Attribution 3.0 License.

Digital Object Identifier (DOI)

http://dx.doi.org/10.18632/oncotarget.3159

Funding Information

This work was supported by grants from, Ministry of Science and Technology No. 2011CB504300 and 2013CB910900, National Nature Science Foundation of China 81202132, 91129303, 81071923, National Key Basic Research 973 Program of China (2013CB910901), and Science and Technology Commission of Shanghai (10140902100).

Repository Citation

Liu, Shuli; Ye, Dongxia; Guo, Wenzheng; Yu, Wenwen; He, Yue; Hu, Jingzhou; Wang, Yanan; Zhang, Ling; Liao, Yueling; Song, Hongyong; Zhong, Shuangshuang; Xu, Dongliang; Yin, Huijing; Sun, Beibei; Wang, Xiaofei; Liu, Jingyi; Wu, Yadi; Zhou, Binhua P.; Zhang, Zhiyuan; and Deng, Jiong, "G9a Is Essential for EMT-Mediated Metastasis and Maintenance of Cancer Stem Cell-Like Characters in Head and Neck Squamous Cell Carcinoma" (2015). Markey Cancer Center Faculty Publications. 50.
https://uknowledge.uky.edu/markey_facpub/50