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Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients.

Zhan J, Niu M, Wang P, Zhu X, Li S, Song J, He H, Wang Y, Xue L, Fang W, Zhang H - Br. J. Cancer (2014)

Bottom Line: 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.Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients.

View Article: PubMed Central - PubMed

Affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.

ABSTRACT

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.

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Related in: MedlinePlus

Expression of HOXB9 in colon adenocarcinoma cell lines and patients. (A) HOXB9 expression in Wooster Cell line data set of oncomine: colorectal cancer cells displayed the highest expression of HOXB9 among 19 types of cancer cell lines included. (B) HOXB9 expression in Bittner Multi-cancer data set of oncomine: colorectal cancer showed the highest expression of HOXB9 in patients among 17 different types of cancer. (C) Left panel: HOXB9 protein levels in colon adenocarcinoma cell lines; right panel: HOXB9 protein levels in breast cancer cell lines. Protein levels of HOXB9 in cell lines were analysed by western blot probed by an anti-HOXB9 monoclonal antibody. Actin was used as loading control. (D) HOXB9 expression in normal colon, intestine and duodenum in mouse. Mouse colon, intestine and duodenum were dissected and tissues were homogenised and quantified. Equal amount of each tissue was used for western blot analysis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control.
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fig1: Expression of HOXB9 in colon adenocarcinoma cell lines and patients. (A) HOXB9 expression in Wooster Cell line data set of oncomine: colorectal cancer cells displayed the highest expression of HOXB9 among 19 types of cancer cell lines included. (B) HOXB9 expression in Bittner Multi-cancer data set of oncomine: colorectal cancer showed the highest expression of HOXB9 in patients among 17 different types of cancer. (C) Left panel: HOXB9 protein levels in colon adenocarcinoma cell lines; right panel: HOXB9 protein levels in breast cancer cell lines. Protein levels of HOXB9 in cell lines were analysed by western blot probed by an anti-HOXB9 monoclonal antibody. Actin was used as loading control. (D) HOXB9 expression in normal colon, intestine and duodenum in mouse. Mouse colon, intestine and duodenum were dissected and tissues were homogenised and quantified. Equal amount of each tissue was used for western blot analysis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control.

Mentions: By reanalysing Oncomine Wooster Cell line data set, we discovered that the expression level of HOXB9 in cell lines from 19 different cancer types and found that cell lines from colon cancer expressed the highest level of HOXB9 among cell lines from other cancer types examined (Figure 1A). Furthermore, we also examined the expression level of HOXB9 in 17 different types of cancer patients in an Oncomine Bittner Multi-cancer data set and found that colon adenocarcinoma expressed the highest level of HOXB9 among cancer patients examined (Figure 1B). Other cancer types including pancreas, prostate and ovary cancers expressed relatively higher level of HOXB9 as well (Figure 1B). In addition, we confirmed the expression of HOXB9 protein in colon adenocarcinoma cell lines (Figure 1C). Interestingly, we also found that HOXB9 is highly expressed in colon but not expressed in intestine and duodenum in mouse (Figure 1D), indicating that HOXB9 might play an important role in the maintenance of the normal structure and function of colonic epithelia. Taken together, these data indicated that HOXB9 is expressed at both RNA and protein levels in cell lines and tumour tissues from both colon adenocarcinoma and normal colon, suggesting that HOXB9 may play a role in colon adenocarcinoma progression.


Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients.

Zhan J, Niu M, Wang P, Zhu X, Li S, Song J, He H, Wang Y, Xue L, Fang W, Zhang H - Br. J. Cancer (2014)

Expression of HOXB9 in colon adenocarcinoma cell lines and patients. (A) HOXB9 expression in Wooster Cell line data set of oncomine: colorectal cancer cells displayed the highest expression of HOXB9 among 19 types of cancer cell lines included. (B) HOXB9 expression in Bittner Multi-cancer data set of oncomine: colorectal cancer showed the highest expression of HOXB9 in patients among 17 different types of cancer. (C) Left panel: HOXB9 protein levels in colon adenocarcinoma cell lines; right panel: HOXB9 protein levels in breast cancer cell lines. Protein levels of HOXB9 in cell lines were analysed by western blot probed by an anti-HOXB9 monoclonal antibody. Actin was used as loading control. (D) HOXB9 expression in normal colon, intestine and duodenum in mouse. Mouse colon, intestine and duodenum were dissected and tissues were homogenised and quantified. Equal amount of each tissue was used for western blot analysis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150282&req=5

fig1: Expression of HOXB9 in colon adenocarcinoma cell lines and patients. (A) HOXB9 expression in Wooster Cell line data set of oncomine: colorectal cancer cells displayed the highest expression of HOXB9 among 19 types of cancer cell lines included. (B) HOXB9 expression in Bittner Multi-cancer data set of oncomine: colorectal cancer showed the highest expression of HOXB9 in patients among 17 different types of cancer. (C) Left panel: HOXB9 protein levels in colon adenocarcinoma cell lines; right panel: HOXB9 protein levels in breast cancer cell lines. Protein levels of HOXB9 in cell lines were analysed by western blot probed by an anti-HOXB9 monoclonal antibody. Actin was used as loading control. (D) HOXB9 expression in normal colon, intestine and duodenum in mouse. Mouse colon, intestine and duodenum were dissected and tissues were homogenised and quantified. Equal amount of each tissue was used for western blot analysis. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as loading control.
Mentions: By reanalysing Oncomine Wooster Cell line data set, we discovered that the expression level of HOXB9 in cell lines from 19 different cancer types and found that cell lines from colon cancer expressed the highest level of HOXB9 among cell lines from other cancer types examined (Figure 1A). Furthermore, we also examined the expression level of HOXB9 in 17 different types of cancer patients in an Oncomine Bittner Multi-cancer data set and found that colon adenocarcinoma expressed the highest level of HOXB9 among cancer patients examined (Figure 1B). Other cancer types including pancreas, prostate and ovary cancers expressed relatively higher level of HOXB9 as well (Figure 1B). In addition, we confirmed the expression of HOXB9 protein in colon adenocarcinoma cell lines (Figure 1C). Interestingly, we also found that HOXB9 is highly expressed in colon but not expressed in intestine and duodenum in mouse (Figure 1D), indicating that HOXB9 might play an important role in the maintenance of the normal structure and function of colonic epithelia. Taken together, these data indicated that HOXB9 is expressed at both RNA and protein levels in cell lines and tumour tissues from both colon adenocarcinoma and normal colon, suggesting that HOXB9 may play a role in colon adenocarcinoma progression.

Bottom Line: 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.Elevated expression of HOXB9 predicts a longer survival in colon adenocarcinoma patients.

View Article: PubMed Central - PubMed

Affiliation: 1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China [3] Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus