Dual role of SnoN in mammalian tumorigenesis.

Dual role of SnoN in mammalian tumorigenesis. Research Abstract Details 

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Dual role of SnoN in mammalian tumorigenesis. Abstract Text:

Qingwei Zhu,Ariel R Krakowski,Elizabeth E Dunham,Long Wang,Abhik Bandyopadhyay,Rebecca Berdeaux,G Steven Martin,LuZhe Sun,Kunxin Luo,

SnoN is an important negative regulator of transforming growth factor beta signaling through its ability to interact with and repress the activity of Smad proteins. It was originally identified as an oncoprotein based on its ability to induce anchorage-independent growth in chicken embryo fibroblasts. However, the roles of SnoN in mammalian epithelial carcinogenesis have not been well defined. Here we show for the first time that SnoN plays an important but complex role in human cancer. SnoN expression is highly elevated in many human cancer cell lines, and this high level of SnoN promotes mitogenic transformation of breast and lung cancer cell lines in vitro and tumor growth in vivo, consistent with its proposed pro-oncogenic role. However, this high level of SnoN expression also inhibits epithelial-to-mesenchymal transdifferentiation. Breast and lung cancer cells expressing the shRNA for SnoN exhibited an increase in cell motility, actin stress fiber formation, metalloprotease activity, and extracellular matrix production as well as a reduction in adherens junction proteins. Supporting this observation, in an in vivo breast cancer metastasis model, reducing SnoN expression was found to moderately enhance metastasis of human breast cancer cells to bone and lung. Thus, SnoN plays both pro-tumorigenic and antitumorigenic roles at different stages of mammalian malignant progression. The growth-promoting activity of SnoN appears to require its ability to bind to and repress the Smad proteins, while the antitumorigenic activity can be mediated by both Smad-dependent and Smad-independent pathways and requires the activity of small GTPase RhoA. Our study has established the importance of SnoN in mammalian epithelial carcinogenesis and revealed a novel aspect of SnoN function in malignant progression.

Dual role of SnoN in mammalian tumorigenesis. Publishing Authors By Initials

Q Zhu,AR Krakowski,EE Dunham,L Wang,A Bandyopadhyay,R Berdeaux,GS Martin,L Sun,K Luo,

For similar enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: rhoa gtp-binding protein research abstracts see: enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: rho gtp-binding proteins: rhoa gtp-binding protein research

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Dual role of SnoN in mammalian tumorigenesis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 324-39

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 30

MONTH: 10

YEAR: 2006

Dual role of SnoN in mammalian tumorigenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8109087

Dual role of SnoN in mammalian tumorigenesis. Keywords Mesh Terms:

KEYWORDS: rhoA GTP-Binding Protein

MESH TERMS: physiology

Chemical & Substance for Abstract: Dual role of SnoN in mammalian tumorigenesis. Information

Substance Name: rhoA GTP-Binding Protein

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for Dual role of SnoN in mammalian tumorigenesis.

AFFILIATION: Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, CA 94720-3204, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 87940

ACRONYM: CA

MEDLINETA: Mol Cell Biol

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