Methylation status of insulin-like growth factor-binding protein 7 concurs with the malignance of oral tongue cancer

Journal of Experimental & Clinical Cancer Research

Ching-Feng Weng³  Wen-Lin Hsu⁵  Yu-Hsuan Wen²  Miao-Chun Yang²  Chia-Fong Lee²  Yu-Fu Chou²  Hon-Yi Lin⁴  Lee-Ping Hsu⁶  Peir-Rong Chen²  Junn-Liang Chang¹  Dai-Wei Liu⁵  Li-Hsuen Chen⁷ 

[1] Department of Biomedical Engineering, Ming Chuan University, Taoyuan, Taiwan;Department of Otolaryngology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan;Department of Life Science and the Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan;Department of Radiation Oncology, Buddhist Dalin Tzu Chi Hospital, Chia-Yi, Taiwan;School of Medicine, Tzu Chi University, Hualien, Taiwan;Department of Otolaryngology, Buddhist Taichung Tzu Chi Hospital, Taichung, Taiwan;Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

关键词: EMT;    Invasion;    Head and neck cancer;    IGFBP-7;   

Others  :  1135982
DOI  :  10.1186/s13046-015-0138-5

 received in 2015-01-15, accepted in 2015-02-16,  发布年份 2015

【 摘 要 】

Background

Aberrant insulin-like growth factor-binding protein 7 (IGFBP-7) expression has been found in various cancers such as prostate, breast, and colon. IGFBP-7 induced the apoptosis of tumor and potentially predicted the clinical outcome in some cancers is further demonstrated. This study investigates the causes and underlying mechanisms of aberrant IGFBP-7 expression in unravelling head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 47 oral tongue cancer patient samples were primarily analyzed for the methylation status in 5′ region of IGFBP-7 by methylation-specific PCR (MS-PCR). Subsequently the invasion, overexpression, and knockdown of IGFBP-7 in the HNSCC A253 invasive subpopulation were employed to examine the effect of IGFBP-7. The epithelial–mesenchymal transition (EMT) marker genes and AKT/GSK3β/β-catenin signaling were further evaluated by Western blot for the understanding the role of aberrant IGFBP-7 expression and thereof putative mechanism.

Results

EMT expressed in the invasive subpopulation of HNSCC cell lines (A253 and RPMI 2650) was contemporary with the down-regulation of IGFBP-7. After treatment with 5-AZA-2′ deoxycytidine, the de-methylated CpG sites in the 5′ region of IGFBP-7 were observed and IGFBP-7 mRNA expression was also restored. Accordingly, re-expression IGFBP-7 in invasive subpopulation of A253 could induce the mesenchymal–epithelial transition (MET) and concurrently inhibited the cell invasion. Moreover, IGFBP-7 methylation status of 47 oral tongue tumors showed a positive correlation to invasive depth of the tumor, loco-regional recurrence, and cancer sequence.

Conclusions

IGFBP-7 can alter EMT relative marker genes and suppress cell invasion in A253 cell through AKT/GSK3β/β-catenin signaling. The epigenetic control of IGFBP-7 in the invasion and metastasis of HNSCC was reported, suggesting that IGFBP-7 could be a prognostic factor for the probability of invasion and a therapeutic remedy.

【 授权许可】

   
2015 Chen et al.; licensee BioMed Central.

【 图 表 】

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