Research Papers:

G9a is essential for EMT-mediated metastasis and maintenance of cancer stem cell-like characters in head and neck squamous cell carcinoma

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

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Oncotarget. 2015; 6:6887-6901. https://doi.org/10.18632/oncotarget.3159

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Shuli Liu1,2, Dongxia Ye1, Wenzheng Guo2, Wenwen Yu1, Yue He1, Jingzhou Hu1, Yanan Wang1, Ling Zhang1, Yueling Liao2,3, Hongyong Song2, Shuangshuang Zhong2, Dongliang Xu2,3, Huijing Yin2, Beibei Sun4, Xiaofei Wang4, Jingyi Liu5, Yadi Wu5, Binhua P. Zhou5, Zhiyuan Zhang1, Jiong Deng2,3,4

1Department of Oral and Maxillofacial–Head and Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

2Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China

4Translation Medicine Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China

5Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY, USA

Correspondence to:

Binhua Zhou, e-mail: [email protected]

Zhiyuan Zhang, e-mail: [email protected]

Jiong Deng, e-mail: [email protected]

Keywords: HNSCC, EMT, lymph node metastasis, cancer stem cell, G9a

Received: October 31, 2014     Accepted: January 17, 2015     Published: January 29, 2015


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.

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