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Journal article
In vivo selection for metastasis promoting genes in the mouse
Proceedings of the National Academy of Sciences - PNAS, v 104(16), pp 6696-6701
17 Apr 2007
PMID: 17420453
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Here, we report the identification of a metastasis promoting factor by a forward genetic screen in mice. A retroviral cDNA library was introduced into the nonmetastatic cancer cell line 168FARN, which was then orthotopically transplanted into mouse mammary fat pads, followed by selection for cells that metastasize to the lung. The genes encoding the disulfide isomerase ERp5 and β-catenin were found to promote breast cancer invasion and metastasis. Disulfide isomerases (thiol isomerases), which catalyze disulfide bond formation, reduction, and isomerization, have not previously been implicated in cancer cell signaling and tumor metastasis. Overexpression of ERp5 promotes both
in vitro
migration and invasion and
in vivo
metastasis of breast cancer cells. These effects were shown to involve activation of ErbB2 and phosphoinositide 3-kinase (PI3K) pathways through dimerization of ErbB2. Activation of ErbB2 and PI3K subsequently stimulates RhoA and β-catenin, which mediate the migration and invasion of tumor cells. Inhibition of ErbB2 and PI3K reverses the phenotypes induced by ERp5. Finally, ERp5 was shown to be up-regulated in human surgical samples of invasive breast cancers. These data identify a link between disulfide isomerases and tumor development, and provide a mechanism that modulates ErbB2 and PI3K signaling in the promotion of cancer progression.
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Details
- Title
- In vivo selection for metastasis promoting genes in the mouse
- Creators
- Kiranmai Gumireddy - The Wistar InstituteFangxian Sun - Genomics Institute of the Novartis Research FoundationAndres J. Klein-Szanto - Fox Chase Cancer CenterJonathan M. Gibbins - University of ReadingPhyllis A. Gimotty - University of PennsylvaniaAleister J. SaundersPeter G. SchultzQihong Huang - The Wistar Institute
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 104(16), pp 6696-6701
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000245869200038
- Scopus ID
- 2-s2.0-34249847158
- Other Identifier
- 991021448026904721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology