A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer Journal Article
| Authors: | Vidal, S.; Rodriguez Bravo, V.; Quinn, S.; Rodriguez-Barrueco, R.; Lujambio, A.; Williams, E.; Sun, X.; delaIglesia-Vicente, J.; Lee, A.; Readhead, B.; Chen, X.; Galsky, M.; Esteve, B.; Petrylak, D.; Dudley, J.; Rabadan, R.; Silva, J.; Hoshida, Y.; Lowe, S.; Cordon-Cardo, C.; Domingo-Domenech, J. |
| Article Title: | A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer |
| Abstract: | Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IGF2 emerged as a mediator of the aggressive properties regulated byGATA2. IGF2 in turn activated IGF1R and INSR as well as a downstream polykinase program. The characterization of this axis prompted a combination strategy whereby dual IGF1R/INSR inhibition restored the efficacy of chemotherapy and improved survival in preclinical models. These studies reveal a GATA2-IGF2 aggressiveness axis in lethal prostate cancer and identify a therapeutic opportunity in this challenging disease. |
| Keywords: | signal transduction; cancer chemotherapy; cancer survival; controlled study; human tissue; major clinical study; cancer growth; drug efficacy; nonhuman; gene expression; tumor volume; animal experiment; animal model; data base; docetaxel; clinical study; carcinogenicity; somatomedin b; circulating tumor cell; castration resistant prostate cancer; receptor upregulation; cabazitaxel; transcription factor gata 2; linsitinib; human; male; priority journal; article |
| Journal Title: | Cancer Cell |
| Volume: | 27 |
| Issue: | 2 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2015-02-09 |
| Start Page: | 223 |
| End Page: | 239 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2014.11.013 |
| PROVIDER: | scopus |
| PUBMED: | 25670080 |
| PMCID: | PMC4356948 |
| DOI/URL: | |
| Notes: | Export Date: 2 March 2015 -- Source: Scopus |
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