Journal
BRITISH JOURNAL OF CANCER
Volume 111, Issue 5, Pages 883-893Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.387
Keywords
HOXB9; colon adenocarcinoma; differentiation; mesenchymal-to-epithelial transition; metastasis
Categories
Funding
- Ministry of Science and Technology of China [2013CB910501, 2010CB912203, 2010CB529402]
- National Natural Science Foundation of China [81230051, 30830048, 31170711, 81321003, 81301802]
- 111 Project of the Ministry of Education
- Beijing Natural Science Foundation [7120002]
- Peking University [BMU20120314, BMU20130364]
- Leading Academic Discipline Project of Beijing Education Bureau
Ask authors/readers for more resources
Background: Little is known about the tumour suppressive proteins and the underlying mechanisms that suppress colon cancer progression. Homeodomain-containing transcription factor HOXB9 plays an important role in embryogenesis and cancer development. We here aim to uncover the potential role of HOXB9 in the regulation of colon adenocarcinoma progression including epithelial-to-mesenchymal transition. Methods: HOXB9 expression in colon adenocarcinoma cells and patients was analysed by western blot and immunohistochemistry separately. Correlation between HOXB9 expressions with patients' survival was assessed by Kaplan-Meier analysis. HOXB9-regulated target gene expression was determined by RNA sequencing in HOXB9-overexpressing colon adenocarcinoma cells. Results: Elevated HOXB9 expression was identified in well-differentiated colon adenocarcinoma patients and was associated with a better overall patients' survival. Overexpression of HOXB9 inhibited colon adenocarcinoma cell growth, migration, invasion in vitro and tumour growth, liver as well as lung metastases in nude mice; whereas silencing HOXB9 promoted these functions. HOXB9 promoted colon adenocarcinoma differentiation via a mechanism that stimulates mesenchymal-to-epithelial transition, involving downregulation of EMT-promoting transcriptional factors including Snail, Twist, FOXC2 and ZEB1 and upregulation of epithelial proteins including E-cadherin, claudins-1, -4, -7, occludin and ZO-1. Conclusions: HOXB9 is a novel tumour suppressor that inhibits colon adenocarcinoma progression by inducing differentiation. Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available