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PMID: 16831886 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition.

The Journal of cell biology ·Vol. 174 ·No. 2 ·2006-07-17 ·Pages 175-83

Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH, Moustakas A

Abstract

Epithelial-mesenchymal transition (EMT) occurs during embryogenesis, carcinoma invasiveness, and metastasis and can be elicited by transforming growth factor-beta (TGF-beta) signaling via intracellular Smad transducers. The molecular mechanisms that control the onset of EMT remain largely unexplored. Transcriptomic analysis revealed that the high mobility group A2 (HMGA2) gene is induced by the Smad pathway during EMT. Endogenous HMGA2 mediates EMT by TGF-beta, whereas ectopic HMGA2 causes irreversible EMT characterized by severe E-cadherin suppression. HMGA2 provides transcriptional input for the expression control of four known regulators of EMT, the zinc-finger proteins Snail and Slug, the basic helix-loop-helix protein Twist, and inhibitor of differentiation 2. We delineate a pathway that links TGF-beta signaling to the control of epithelial differentiation via HMGA2 and a cohort of major regulators of tumor invasiveness and metastasis. This network of signaling/transcription factors that work sequentially to establish EMT suggests that combinatorial detection of these proteins could serve as a new tool for EMT analysis in cancer patients.

MeSH Terms
Animals Cell Proliferation/drug effects Epithelial Cells/cytology,drug effects Gene Expression Regulation/drug effects HMGA2 Protein/genetics,metabolism Humans Mesoderm/cytology,drug effects Mice RNA, Messenger/genetics,metabolism Signal Transduction/drug effects Smad Proteins/metabolism Transcription, Genetic/drug effects Transforming Growth Factor beta/pharmacology
Chemicals
HMGA2 Protein RNA, Messenger Smad Proteins Transforming Growth Factor beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Thuault Sylvie
Ludwig Institute for Cancer Research, Uppsala University, SE-751 24 Uppsala, Sweden, and Institut National de la Santé et de la Recherche Médicale, Hôpital E. Herriot, Lyon Cedex, France.
Valcourt Ulrich
Petersen Maj
Manfioletti Guidalberto
Heldin Carl-Henrik
Moustakas Aristidis
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200512110
Published
2006-07-17
Epub
2006-00-10
Pages
175-83
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064178
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200512110 PMC Full Text View journal details
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