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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 3/2013

01-03-2013 | Original Article

HMGA2 Elicits EMT by Activating the Wnt/β-catenin Pathway in Gastric Cancer

Authors: Lang Zha, Jing Zhang, Weixue Tang, Neng Zhang, Miao He, Yi Guo, Ziwei Wang

Published in: Digestive Diseases and Sciences | Issue 3/2013

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Abstract

Background

The high mobility group protein A2 (HMGA2) is an architectural transcription factor that plays an important role in the development and progression of many malignant neoplasms. High expression of HMGA2 in gastric cancer correlates with invasiveness of cancer and is an independent prognostic factor. The reason for this might be HMGA2 promoting epithelial–mesenchymal transitions (EMT), which is the key process of metastasis for some underlying mechanisms.

Aims

This study was designed to test whether HMGA2 participates in the EMT and to further understand the underlying mechanisms of EMT promoted by HMGA2.

Methods

We examined the cell biology and molecular biology changes after overexpression and knockdown HMGA2 of gastric cancer cells in vitro and vivo. To further understand the underlying mechanisms of EMT promoted by HMGA2, based on our previous study, we examined the changes of target genes of HMGA2 after overexpression and knockdown HMGA2 of gastric cancer cells.

Results

The results indicated that overexpressing HMGA2 enabled enhancing the oncogenic properties of gastric epithelial origin cell in vitro and in vivo. Furthermore, our study showed that HMGA2 was able to elicit EMT and regulate several genes which are closely related to the Wnt/β-catenin pathway by directly binding to their promoter thereby activating the Wnt/β-catenin pathway.

Conclusions

The Wnt/β-catenin pathway activated by HMGA2 might be the underlying mechanism of EMT in gastric cancer cells.
Literature
1.
Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
2.
Wu Y, Zhou BP. New insights of epithelial–mesenchymal transition in cancer metastasis. Acta Biochim Biophys Sin (Shanghai). 2008;40:643–650.CrossRef
3.
Fuxe J, Vincent T, Garcia de Herreros A. Transcriptional crosstalk between TGF-beta and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle. 2010;9:2363–2374.PubMedCrossRef
4.
Bates RC, Mercurio AM. The epithelial–mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 2005;4:365–370.PubMedCrossRef
5.
Thiery JP, Acloque H, Huang RY, et al. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139:871–890.PubMedCrossRef
6.
Eramo A, Haas TL, De Maria R. Lung cancer stem cells: tools and targets to fight lung cancer. Oncogene. 2010;29:4625–4635.PubMedCrossRef
7.
Kratz JR, Yagui-Beltran A, Jablons DM. Cancer stem cells in lung tumorigenesis. Ann Thorac Surg. 2010;89:S2090–S2095.PubMedCrossRef
8.
9.
Biddle A, Liang X, Gammon L, et al. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res. 2011;71:5317–5326.PubMedCrossRef
10.
Chen C, Wei Y, Hummel M, et al. Evidence for epithelial–mesenchymal transition in cancer stem cells of head and neck squamous cell carcinoma. PLoS One. 2011;6:e16466.PubMedCrossRef
11.
Mani SA, Guo W, Liao MJ, et al. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–715.PubMedCrossRef
12.
Hock R, Furusawa T, Ueda T, et al. HMG chromosomal proteins in development and disease. Trends Cell Biol. 2007;17:72–79.PubMedCrossRef
13.
Meyer B, Loeschke S, Schultze A, et al. HMGA2 overexpression in non-small cell lung cancer. Mol Carcinog. 2007;46:503–511.PubMedCrossRef
14.
Langelotz C, Schmid P, Jakob C, et al. Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer. Br J Cancer. 2003;88:1406–1410.PubMedCrossRef
15.
Belge G, Meyer A, Klemke M, et al. Upregulation of HMGA2 in thyroid carcinomas: a novel molecular marker to distinguish between benign and malignant follicular neoplasias. Genes Chromosom Cancer. 2008;47:56–63.PubMedCrossRef
16.
Motoyama K, Inoue H, Nakamura Y, et al. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res. 2008;14:2334–2340.PubMedCrossRef
17.
Miyazawa J, Mitoro A, Kawashiri S, et al. Expression of mesenchyme-specific gene HMGA2 in squamous cell carcinomas of the oral cavity. Cancer Res. 2004;64:2024–2029.PubMedCrossRef
18.
Thuault S, Valcourt U, Petersen M, et al. Transforming growth factor-beta employs HMGA2 to elicit epithelial–mesenchymal transition. J Cell Biol. 2006;174:175–183.PubMedCrossRef
19.
Watanabe S, Ueda Y, Akaboshi S, et al. HMGA2 maintains oncogenic RAS-induced epithelial–mesenchymal transition in human pancreatic cancer cells. Am J Pathol. 2009;174:854–868.PubMedCrossRef
20.
Wu J, Liu Z, Shao C, et al. HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes. Cancer Res. 2011;71:349–359.PubMedCrossRef
21.
Nishino J, Kim I, Chada K, et al. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell. 2008;135:227–239.PubMedCrossRef
22.
Yu F, Yao H, Zhu P, et al. let-7 Regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–1123.PubMedCrossRef
23.
Zha L, Wang Z, Tang W, et al. Genome-wide analysis of HMGA2 transcription factor binding sites by ChIP on chip in gastric carcinoma cells. Mol Cell Biochem. 2012;364:243–251.PubMedCrossRef
24.
Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–454.PubMedCrossRef
25.
Khan NP, Pandith AA, Hussain MU, et al. Novelty of Axin 2 and lack of Axin 1 gene mutation in colorectal cancer: a study in Kashmiri population. Mol Cell Biochem. 2011;355:149–155.PubMedCrossRef
26.
27.
Schoenmakers EF, Wanschura S, Mols R, et al. Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours. Nat Genet. 1995;10:436–444.PubMedCrossRef
28.
Pozharskaya V, Torres-Gonzalez E, Rojas M, et al. Twist: a regulator of epithelial-mesenchymal transition in lung fibrosis. PLoS One. 2009;4:e7559.PubMedCrossRef
29.
Yu L, Li HZ, Lu SM, et al. Down-regulation of TWIST decreases migration and invasion of laryngeal carcinoma Hep-2 cells by regulating the E-cadherin, N-cadherin expression. J Cancer Res Clin Oncol. 2011;137:1487–1493.PubMedCrossRef
30.
Pfannkuche K, Summer H, Li O, et al. The high mobility group protein HMGA2: a co-regulator of chromatin structure and pluripotency in stem cells? Stem Cell Rev. 2009;5:224–230.PubMedCrossRef
Metadata
Title
HMGA2 Elicits EMT by Activating the Wnt/β-catenin Pathway in Gastric Cancer
Authors
Lang Zha
Jing Zhang
Weixue Tang
Neng Zhang
Miao He
Yi Guo
Ziwei Wang
Publication date
01-03-2013
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 3/2013
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-012-2399-6

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