دورية أكاديمية
Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes.
| العنوان: | Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes. |
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| المؤلفون: | Jeffrey J Wallin, Jane Guan, Kyle A Edgar, Wei Zhou, Ross Francis, Anthony C Torres, Peter M Haverty, Jeffrey Eastham-Anderson, Sabrina Arena, Alberto Bardelli, Sue Griffin, John E Goodall, Kyla M Grimshaw, Klaus P Hoeflich, Christopher Torrance, Marcia Belvin, Lori S Friedman |
| المصدر: | PLoS ONE, Vol 7, Iss 5, p e36402 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | The PTEN/PI3K pathway is commonly mutated in cancer and therefore represents an attractive target for therapeutic intervention. To investigate the primary phenotypes mediated by increased pathway signaling in a clean, patient-relevant context, an activating PIK3CA mutation (H1047R) was knocked-in to an endogenous allele of the MCF10A non-tumorigenic human breast epithelial cell line. Introduction of an endogenously mutated PIK3CA allele resulted in a marked epithelial-mesenchymal transition (EMT) and invasive phenotype, compared to isogenic wild-type cells. The invasive phenotype was linked to enhanced PIP(3) production via a S6K-IRS positive feedback mechanism. Moreover, potent and selective inhibitors of PI3K were highly effective in reversing this phenotype, which is optimally revealed in 3-dimensional cell culture. In contrast, inhibition of Akt or mTOR exacerbated the invasive phenotype. Our results suggest that invasion is a core phenotype mediated by increased PTEN/PI3K pathway activity and that therapeutic agents targeting different nodes of the PI3K pathway may have dramatic differences in their ability to reverse or promote cancer metastasis. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22570710/?tool=EBI; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0036402 |
| URL الوصول: | https://doaj.org/article/64952bf9ee0a4f75af0606c666386285 |
| رقم الأكسشن: | edsdoj.64952bf9ee0a4f75af0606c666386285 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0036402 |