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.
1] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Health Science Center, Beijing 100191, China [2] Laboratory of Molecular Pathology, Department of Pathology, Peking University Health Science Center, Beijing 100191, China.
Br J Cancer. 2014 Aug 26;111(5):883-93. doi: 10.1038/bjc.2014.387. Epub 2014 Jul 15.
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.
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.
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.
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.
关于抑制结肠癌进展的肿瘤抑制蛋白及其潜在机制知之甚少。同源盒转录因子 HOXB9 在胚胎发生和癌症发展中发挥着重要作用。我们旨在揭示 HOXB9 在调节结肠腺癌进展（包括上皮间质转化）中的潜在作用。
通过 Western blot 和免疫组织化学分别分析结肠腺癌细胞和患者中 HOXB9 的表达。通过 Kaplan-Meier 分析评估 HOXB9 表达与患者生存的相关性。通过在 HOXB9 过表达的结肠腺癌细胞中进行 RNA 测序确定 HOXB9 调节的靶基因表达。
在分化良好的结肠腺癌患者中发现 HOXB9 表达升高，与患者总体生存较好相关。HOXB9 的过表达抑制了结肠腺癌细胞的体外生长、迁移和侵袭以及裸鼠肿瘤生长、肝转移和肺转移；而沉默 HOXB9 则促进了这些功能。HOXB9 通过刺激间充质上皮转化的机制促进结肠腺癌分化，涉及下调 EMT 促进转录因子，包括 Snail、Twist、FOXC2 和 ZEB1，以及上调上皮蛋白，包括 E-cadherin、claudin-1、-4、-7、occludin 和 ZO-1。
HOXB9 是一种新型肿瘤抑制因子，通过诱导分化抑制结肠腺癌进展。HOXB9 表达升高预示着结肠腺癌患者的生存时间更长。
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