help button home button Am J Pathol Epitomics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2009.080523 on January 29, 2009

Published online before print January 29, 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2009.080523v1
174/3/854    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watanabe, S.
Right arrow Articles by Nakao, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, S.
Right arrow Articles by Nakao, M.
(American Journal of Pathology. 2009;174:854-868.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080523

HMGA2 Maintains Oncogenic RAS-Induced Epithelial-Mesenchymal Transition in Human Pancreatic Cancer Cells

Sugiko Watanabe, Yasuaki Ueda, Shin-ichi Akaboshi, Yuko Hino, Yoko Sekita and Mitsuyoshi Nakao

From the Department of Regeneration Medicine, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan

Pancreatic cancer is a highly aggressive malignancy due to elevated mitotic activities and epithelial-mesenchymal transition (EMT). Oncogenic RAS and transforming growth factor-β signaling are implicated in these malignant features. The mechanisms that underlie EMT need to be addressed since it promotes tissue invasion and metastasis. The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor that is primarily expressed in undifferentiated tissues and tumors of mesenchymal origin. However, its role in EMT in pancreatic cancer is largely unknown. Here we report that HMGA2 is involved in EMT maintenance in human pancreatic cancer cells. Specific knockdown of HMGA2 inhibited cell proliferation, leading to an epithelial-state transition that restores cell-cell contact due to E-cadherin up-regulation. Consistently, an inverse correlation between HMGA2-positive cells and E-cadherin-positive cells was found in cancer tissues. Inhibition of the RAS/MEK pathway also induced an epithelial transition, together with HMGA2 down-regulation. Transcriptional repressors of the E-cadherin gene, such as SNAIL, decreased after HMGA2 knockdown since HMGA2 directly activated the SNAlL gene promoter. The decrease of SNAIL after RAS/MEK inhibition was suppressed by HMGA2 overexpression. Further, let-7 microRNA-mediated HMGA2 down-regulation had no effect on the prevention of the transformed phenotype in these cells. These data shed light on the importance of HMGA2 in reversibly maintaining EMT, suggesting that HMGA2 is a potential therapeutic target for the treatment of pancreatic cancer.




This article has been cited by other articles:


Home page
 Endocr Relat CancerHome page
B. Boyerinas, S.-M. Park, A. Hau, A. E Murmann, and M. E Peter
The role of let-7 in cell differentiation and cancer
Endocr. Relat. Cancer, March 1, 2010; 17(1): F19 - F36.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S.-i. Akaboshi, S. Watanabe, Y. Hino, Y. Sekita, Y. Xi, K. Araki, K.-i. Yamamura, M. Oshima, T. Ito, H. Baba, et al.
HMGA1 Is Induced by Wnt/{beta}-Catenin Pathway and Maintains Cell Proliferation in Gastric Cancer
Am. J. Pathol., October 1, 2009; 175(4): 1675 - 1685.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American Society for Investigative Pathology.