HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif

HOXB9, a transcription factor, plays an important role in development. While HOXB9 has been implicated in tumorigenesis and metastasis, its mechanisms are variable and its role in gastric carcinoma (GC) remains unclear. In the present study, we demonstrated that the expression of HOXB9 decreased in...

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Main Authors:	Chang, Qing, Zhang, Li, He, Changyu, Zhang, Baogui, Zhang, Jun, Liu, Bingya, Zeng, Naiyan, Zhu, Zhenggang
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767475/

id	pubmed-4767475
recordtype	oai_dc
spelling	pubmed-47674752016-03-25 HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif Chang, Qing Zhang, Li He, Changyu Zhang, Baogui Zhang, Jun Liu, Bingya Zeng, Naiyan Zhu, Zhenggang Research Paper HOXB9, a transcription factor, plays an important role in development. While HOXB9 has been implicated in tumorigenesis and metastasis, its mechanisms are variable and its role in gastric carcinoma (GC) remains unclear. In the present study, we demonstrated that the expression of HOXB9 decreased in gastric carcinoma and was associated with malignancy and metastasis. Re-expression of HOXB9 in gastric cell lines resulted in the suppression of cell proliferation, migration, and invasion, which was accompanied by the induction of mesenchymal-to-epithelial transition (MET). Comparative sequence analysis and examination of a HOXB9 structural model indicated that three sites might possibly be involved in MET regulation. The in vitro study of HOXB9 mutants showed that these were unable to inhibit MET induction. However, when overexpressing a HOXB9 mutant lacking the hexapeptide motif, a more potent MET induction and tumor suppression was observed compared to that of the wild-type, indicating that the presence of the hexapeptide motif reduced HOXB9 MET induction and tumor suppression activity. Therefore, the results of the present study suggested that HOXB9 is a tumor suppressor in gastric carcinoma, and its activity was controlled by different regulatory mechanisms such as the hexapeptide motif as a “brake” in this case. The results of these regulatory effects could lead to either oncogenic or tumor suppressive roles of HOXB9, depending on the context of the particular type of cancer involved. Impact Journals LLC 2015-10-23 /pmc/articles/PMC4767475/ /pubmed/26536658 Text en Copyright: © 2015 Chang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Chang, Qing Zhang, Li He, Changyu Zhang, Baogui Zhang, Jun Liu, Bingya Zeng, Naiyan Zhu, Zhenggang
spellingShingle	Chang, Qing Zhang, Li He, Changyu Zhang, Baogui Zhang, Jun Liu, Bingya Zeng, Naiyan Zhu, Zhenggang HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
author_facet	Chang, Qing Zhang, Li He, Changyu Zhang, Baogui Zhang, Jun Liu, Bingya Zeng, Naiyan Zhu, Zhenggang
author_sort	Chang, Qing
title	HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
title_short	HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
title_full	HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
title_fullStr	HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
title_full_unstemmed	HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
title_sort	hoxb9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif
description	HOXB9, a transcription factor, plays an important role in development. While HOXB9 has been implicated in tumorigenesis and metastasis, its mechanisms are variable and its role in gastric carcinoma (GC) remains unclear. In the present study, we demonstrated that the expression of HOXB9 decreased in gastric carcinoma and was associated with malignancy and metastasis. Re-expression of HOXB9 in gastric cell lines resulted in the suppression of cell proliferation, migration, and invasion, which was accompanied by the induction of mesenchymal-to-epithelial transition (MET). Comparative sequence analysis and examination of a HOXB9 structural model indicated that three sites might possibly be involved in MET regulation. The in vitro study of HOXB9 mutants showed that these were unable to inhibit MET induction. However, when overexpressing a HOXB9 mutant lacking the hexapeptide motif, a more potent MET induction and tumor suppression was observed compared to that of the wild-type, indicating that the presence of the hexapeptide motif reduced HOXB9 MET induction and tumor suppression activity. Therefore, the results of the present study suggested that HOXB9 is a tumor suppressor in gastric carcinoma, and its activity was controlled by different regulatory mechanisms such as the hexapeptide motif as a “brake” in this case. The results of these regulatory effects could lead to either oncogenic or tumor suppressive roles of HOXB9, depending on the context of the particular type of cancer involved.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767475/
_version_	1613543402892165120

HOXB9 induction of mesenchymal-to-epithelial transition in gastric carcinoma is negatively regulated by its hexapeptide motif

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