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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Li-Hsuen Chen, Dai-Wei Liu, Junn-Liang Chang, Peir-Rong Chen, Lee-Ping Hsu, Hon-Yi Lin, Yu-Fu Chou, Chia-Fong Lee, Miao-Chun Yang, Yu-Hsuan Wen, Wen-Lin Hsu, Ching-Feng Weng

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2015

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Abstract

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.
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Metadata
Title
Methylation status of insulin-like growth factor-binding protein 7 concurs with the malignance of oral tongue cancer
Authors
Li-Hsuen Chen
Dai-Wei Liu
Junn-Liang Chang
Peir-Rong Chen
Lee-Ping Hsu
Hon-Yi Lin
Yu-Fu Chou
Chia-Fong Lee
Miao-Chun Yang
Yu-Hsuan Wen
Wen-Lin Hsu
Ching-Feng Weng
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2015
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-015-0138-5

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